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Adjuvant ET lowers distant metastases risk in ER+ /HER2− T1a/bN0M0 BC
Key clinical point: Adjuvant endocrine therapy (ET) significantly reduces the incidence of distant metastasis in patients with estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2−) T1a/bN0M0 breast cancer (BC).
Major finding: The 9-year cumulative incidence of distant metastasis was significantly lower in patients who did vs did not receive adjuvant ET (1.5% vs 2.6%; adjusted subdistribution hazard ratio 0.54; P = .027), with the risk factors for distant metastasis being mastectomy (P = .022), no prior receipt of ET (P = .027), lymphatic invasion (P = .004), and higher nuclear grade (P = .047).
Study details: Findings are from a multicenter cohort study including 4758 patients with ER+ /HER2− T1a/bN0M0 BC who underwent surgery, of whom 3991 patients were administered adjuvant ET.
Disclosures: This study was partly supported by the National Cancer Center Research and Development Fund and the Practical Research for Innovative Cancer Control, Japan. The authors declared no conflicts of interest.
Source: Sasada S et al. Prognostic impact of adjuvant endocrine therapy for estrogen receptor-positive and HER2-negative T1a/bN0M0 breast cancer. Breast Cancer Res Treat. 2023 (Sep 9). doi: 10.1007/s10549-023-07097-6
Key clinical point: Adjuvant endocrine therapy (ET) significantly reduces the incidence of distant metastasis in patients with estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2−) T1a/bN0M0 breast cancer (BC).
Major finding: The 9-year cumulative incidence of distant metastasis was significantly lower in patients who did vs did not receive adjuvant ET (1.5% vs 2.6%; adjusted subdistribution hazard ratio 0.54; P = .027), with the risk factors for distant metastasis being mastectomy (P = .022), no prior receipt of ET (P = .027), lymphatic invasion (P = .004), and higher nuclear grade (P = .047).
Study details: Findings are from a multicenter cohort study including 4758 patients with ER+ /HER2− T1a/bN0M0 BC who underwent surgery, of whom 3991 patients were administered adjuvant ET.
Disclosures: This study was partly supported by the National Cancer Center Research and Development Fund and the Practical Research for Innovative Cancer Control, Japan. The authors declared no conflicts of interest.
Source: Sasada S et al. Prognostic impact of adjuvant endocrine therapy for estrogen receptor-positive and HER2-negative T1a/bN0M0 breast cancer. Breast Cancer Res Treat. 2023 (Sep 9). doi: 10.1007/s10549-023-07097-6
Key clinical point: Adjuvant endocrine therapy (ET) significantly reduces the incidence of distant metastasis in patients with estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2−) T1a/bN0M0 breast cancer (BC).
Major finding: The 9-year cumulative incidence of distant metastasis was significantly lower in patients who did vs did not receive adjuvant ET (1.5% vs 2.6%; adjusted subdistribution hazard ratio 0.54; P = .027), with the risk factors for distant metastasis being mastectomy (P = .022), no prior receipt of ET (P = .027), lymphatic invasion (P = .004), and higher nuclear grade (P = .047).
Study details: Findings are from a multicenter cohort study including 4758 patients with ER+ /HER2− T1a/bN0M0 BC who underwent surgery, of whom 3991 patients were administered adjuvant ET.
Disclosures: This study was partly supported by the National Cancer Center Research and Development Fund and the Practical Research for Innovative Cancer Control, Japan. The authors declared no conflicts of interest.
Source: Sasada S et al. Prognostic impact of adjuvant endocrine therapy for estrogen receptor-positive and HER2-negative T1a/bN0M0 breast cancer. Breast Cancer Res Treat. 2023 (Sep 9). doi: 10.1007/s10549-023-07097-6
BRCA-altered TNBC: High-dose alkylating chemotherapy fails to show improvement in phase 3 study
Key clinical point: Neoadjuvant high-dose alkylating chemotherapy did not improve the Neoadjuvant Response Index (NRI) scores in patients with BRCA1- or BRCA2-pathway-altered (BRCA-altered) triple-negative breast cancer (TNBC).
Major finding: The NRI scores were comparable between the conventional and high-dose chemotherapy treatment groups (0.72 vs 0.78; P = .41). Adverse events, such as fatigue, infections, nausea, oral mucositis, and diarrhea, were more prevalent in the high-dose vs conventional chemotherapy group, although no treatment-related deaths occurred in either group.
Study details: Findings are from the phase 3 neo-TN study that included 122 patients with BRCA-altered TNBC who were randomly assigned to receive either conventional or high-dose chemotherapy.
Disclosures: This study was supported by The Dutch Cancer Foundation and the Schumacher Kramer Foundation, Amsterdam. The authors declared no conflicts of interest.
Source: Vliek S et al. High-dose alkylating chemotherapy in BRCA-altered triple-negative breast cancer: The randomized phase III NeoTN trial. NPJ Breast Cancer. 2023;9:75 (Sep 9). doi: 10.1038/s41523-023-00580-9
Key clinical point: Neoadjuvant high-dose alkylating chemotherapy did not improve the Neoadjuvant Response Index (NRI) scores in patients with BRCA1- or BRCA2-pathway-altered (BRCA-altered) triple-negative breast cancer (TNBC).
Major finding: The NRI scores were comparable between the conventional and high-dose chemotherapy treatment groups (0.72 vs 0.78; P = .41). Adverse events, such as fatigue, infections, nausea, oral mucositis, and diarrhea, were more prevalent in the high-dose vs conventional chemotherapy group, although no treatment-related deaths occurred in either group.
Study details: Findings are from the phase 3 neo-TN study that included 122 patients with BRCA-altered TNBC who were randomly assigned to receive either conventional or high-dose chemotherapy.
Disclosures: This study was supported by The Dutch Cancer Foundation and the Schumacher Kramer Foundation, Amsterdam. The authors declared no conflicts of interest.
Source: Vliek S et al. High-dose alkylating chemotherapy in BRCA-altered triple-negative breast cancer: The randomized phase III NeoTN trial. NPJ Breast Cancer. 2023;9:75 (Sep 9). doi: 10.1038/s41523-023-00580-9
Key clinical point: Neoadjuvant high-dose alkylating chemotherapy did not improve the Neoadjuvant Response Index (NRI) scores in patients with BRCA1- or BRCA2-pathway-altered (BRCA-altered) triple-negative breast cancer (TNBC).
Major finding: The NRI scores were comparable between the conventional and high-dose chemotherapy treatment groups (0.72 vs 0.78; P = .41). Adverse events, such as fatigue, infections, nausea, oral mucositis, and diarrhea, were more prevalent in the high-dose vs conventional chemotherapy group, although no treatment-related deaths occurred in either group.
Study details: Findings are from the phase 3 neo-TN study that included 122 patients with BRCA-altered TNBC who were randomly assigned to receive either conventional or high-dose chemotherapy.
Disclosures: This study was supported by The Dutch Cancer Foundation and the Schumacher Kramer Foundation, Amsterdam. The authors declared no conflicts of interest.
Source: Vliek S et al. High-dose alkylating chemotherapy in BRCA-altered triple-negative breast cancer: The randomized phase III NeoTN trial. NPJ Breast Cancer. 2023;9:75 (Sep 9). doi: 10.1038/s41523-023-00580-9
High temporal and spatial resolution improves BC detection in women with high background parenchymal enhancement
Key clinical point: In women with high levels of background parenchymal enhancement (BPE), a simultaneous high-temporal/high-spatial resolution (HTHS) magnetic resonance imaging (MRI) protocol detected an additional 15.7 cases of breast cancer (BC) per 1000 patients than the standard high-spatial resolution MRI protocol while concomitantly decreasing the rate of unnecessary biopsies by ~10%.
Major finding: HTHS vs standard protocol improved the BC detection rate per 1000 patients (23.6 vs 7.9; P = .021), increased the positive predictive value of biopsy (16.0% vs 6.3%; P = .014), and decreased the rate of unnecessary biopsies by 9.8%.
Study details: This retrospective study included 1414 women with 1481 high-BPE examinations.
Disclosures: This study was supported partly by the US National Cancer Institute. JS Sung, K Feigin, and K Pinker declared serving in leadership roles and consulting roles or as members of speakers’ bureaus of or receiving research funding from various sources.
Source: Eskreis-Winkler S et al. High-temporal/high-spatial resolution breast magnetic resonance imaging improves diagnostic accuracy compared with standard breast magnetic resonance imaging in patients with high background parenchymal enhancement. J Clin Oncol. 2023 (Aug 10). doi: 10.1200/JCO.22.00635
Key clinical point: In women with high levels of background parenchymal enhancement (BPE), a simultaneous high-temporal/high-spatial resolution (HTHS) magnetic resonance imaging (MRI) protocol detected an additional 15.7 cases of breast cancer (BC) per 1000 patients than the standard high-spatial resolution MRI protocol while concomitantly decreasing the rate of unnecessary biopsies by ~10%.
Major finding: HTHS vs standard protocol improved the BC detection rate per 1000 patients (23.6 vs 7.9; P = .021), increased the positive predictive value of biopsy (16.0% vs 6.3%; P = .014), and decreased the rate of unnecessary biopsies by 9.8%.
Study details: This retrospective study included 1414 women with 1481 high-BPE examinations.
Disclosures: This study was supported partly by the US National Cancer Institute. JS Sung, K Feigin, and K Pinker declared serving in leadership roles and consulting roles or as members of speakers’ bureaus of or receiving research funding from various sources.
Source: Eskreis-Winkler S et al. High-temporal/high-spatial resolution breast magnetic resonance imaging improves diagnostic accuracy compared with standard breast magnetic resonance imaging in patients with high background parenchymal enhancement. J Clin Oncol. 2023 (Aug 10). doi: 10.1200/JCO.22.00635
Key clinical point: In women with high levels of background parenchymal enhancement (BPE), a simultaneous high-temporal/high-spatial resolution (HTHS) magnetic resonance imaging (MRI) protocol detected an additional 15.7 cases of breast cancer (BC) per 1000 patients than the standard high-spatial resolution MRI protocol while concomitantly decreasing the rate of unnecessary biopsies by ~10%.
Major finding: HTHS vs standard protocol improved the BC detection rate per 1000 patients (23.6 vs 7.9; P = .021), increased the positive predictive value of biopsy (16.0% vs 6.3%; P = .014), and decreased the rate of unnecessary biopsies by 9.8%.
Study details: This retrospective study included 1414 women with 1481 high-BPE examinations.
Disclosures: This study was supported partly by the US National Cancer Institute. JS Sung, K Feigin, and K Pinker declared serving in leadership roles and consulting roles or as members of speakers’ bureaus of or receiving research funding from various sources.
Source: Eskreis-Winkler S et al. High-temporal/high-spatial resolution breast magnetic resonance imaging improves diagnostic accuracy compared with standard breast magnetic resonance imaging in patients with high background parenchymal enhancement. J Clin Oncol. 2023 (Aug 10). doi: 10.1200/JCO.22.00635
TNBC: Greater efficacy of neoadjuvant apatinib + dose-dense paclitaxel + carboplatin vs dose-dense paclitaxel + carboplatin
Key clinical point: In patients with locally advanced triple-negative breast cancer (TNBC), neoadjuvant apatinib (Apa) plus dose-dense paclitaxel and carboplatin (ddTCb) was more effective in improving clinical outcomes than ddTCb alone and showed an acceptable safety profile.
Major finding: A significantly higher proportion of patients in the Apa + ddTCb vs ddTCb treatment group achieved pathological complete response (60.9% vs 30.4%; P = .009) and underwent breast-conserving surgery (47.8% vs 21.7%; P = .016). The incidence of adverse events was higher in the Apa + ddTCb treatment arm, but they were generally acceptable.
Study details: This prospective cohort study included 23 patients with stages I-IIIC TNBC who received neoadjuvant Apa + ddTCb therapy matched with 69 patients with stages I-IIIC TNBC who received neoadjuvant ddTCb therapy only.
Disclosures: This study was supported by CAMS Innovation Fund for Medical Sciences and the Translational research project of Medical Oncology Key Foundation of Cancer Hospital, Chinese Academy of Medical Sciences. The authors declared no conflicts of interest.
Source: Liu J, Xu B, Zhang P, et al. Efficacy and safety of apatinib combined with dose-dense paclitaxel and carboplatin in neoadjuvant therapy for locally advanced triple-negative breast cancer: A prospective cohort study with propensity-matched analysis. Int J Cancer. 2023 (Sep 7). doi: 10.1002/ijc.34717
Key clinical point: In patients with locally advanced triple-negative breast cancer (TNBC), neoadjuvant apatinib (Apa) plus dose-dense paclitaxel and carboplatin (ddTCb) was more effective in improving clinical outcomes than ddTCb alone and showed an acceptable safety profile.
Major finding: A significantly higher proportion of patients in the Apa + ddTCb vs ddTCb treatment group achieved pathological complete response (60.9% vs 30.4%; P = .009) and underwent breast-conserving surgery (47.8% vs 21.7%; P = .016). The incidence of adverse events was higher in the Apa + ddTCb treatment arm, but they were generally acceptable.
Study details: This prospective cohort study included 23 patients with stages I-IIIC TNBC who received neoadjuvant Apa + ddTCb therapy matched with 69 patients with stages I-IIIC TNBC who received neoadjuvant ddTCb therapy only.
Disclosures: This study was supported by CAMS Innovation Fund for Medical Sciences and the Translational research project of Medical Oncology Key Foundation of Cancer Hospital, Chinese Academy of Medical Sciences. The authors declared no conflicts of interest.
Source: Liu J, Xu B, Zhang P, et al. Efficacy and safety of apatinib combined with dose-dense paclitaxel and carboplatin in neoadjuvant therapy for locally advanced triple-negative breast cancer: A prospective cohort study with propensity-matched analysis. Int J Cancer. 2023 (Sep 7). doi: 10.1002/ijc.34717
Key clinical point: In patients with locally advanced triple-negative breast cancer (TNBC), neoadjuvant apatinib (Apa) plus dose-dense paclitaxel and carboplatin (ddTCb) was more effective in improving clinical outcomes than ddTCb alone and showed an acceptable safety profile.
Major finding: A significantly higher proportion of patients in the Apa + ddTCb vs ddTCb treatment group achieved pathological complete response (60.9% vs 30.4%; P = .009) and underwent breast-conserving surgery (47.8% vs 21.7%; P = .016). The incidence of adverse events was higher in the Apa + ddTCb treatment arm, but they were generally acceptable.
Study details: This prospective cohort study included 23 patients with stages I-IIIC TNBC who received neoadjuvant Apa + ddTCb therapy matched with 69 patients with stages I-IIIC TNBC who received neoadjuvant ddTCb therapy only.
Disclosures: This study was supported by CAMS Innovation Fund for Medical Sciences and the Translational research project of Medical Oncology Key Foundation of Cancer Hospital, Chinese Academy of Medical Sciences. The authors declared no conflicts of interest.
Source: Liu J, Xu B, Zhang P, et al. Efficacy and safety of apatinib combined with dose-dense paclitaxel and carboplatin in neoadjuvant therapy for locally advanced triple-negative breast cancer: A prospective cohort study with propensity-matched analysis. Int J Cancer. 2023 (Sep 7). doi: 10.1002/ijc.34717
Metastatic BC: Meaningful clinical benefit with trifluridine/tipiracil in phase 2 study
Key clinical point: Trifluridine/tipiracil (FTD/TPI) showed promising anti-tumor activity with a manageable safety profile regardless of prior exposure to fluoropyrimidine therapy in patients with metastatic breast cancer (BC).
Major finding: The median durations of progression-free survival were 5.7 months and 9.4 months in patients with and without prior exposure to fluoropyrimidine therapy, respectively. Neutropenia (81.8%), fatigue (29.7%), anorexia (25.7%), and nausea (25.7%) were the most common all-grade treatment-related adverse events.
Study details: Findings are from a phase 2 study including 74 patients with metastatic BC with or without prior exposure to fluoropyrimidine therapy who received FTD/TPI.
Disclosures: This study was funded by a grant from the National Medical Research Council, Singapore. Some authors declared receiving research funding, honoraria, consulting fees, or travel support from or having other ties with various sources.
Source: Lim JSJ et al. Phase II study of trifluridine/tipiracil (FTD/TPI) in metastatic breast cancers with or without prior exposure to fluoropyrimidines. Eur J Cancer. 2023;113311 (Aug 25). doi: 10.1016/j.ejca.2023.113311
Key clinical point: Trifluridine/tipiracil (FTD/TPI) showed promising anti-tumor activity with a manageable safety profile regardless of prior exposure to fluoropyrimidine therapy in patients with metastatic breast cancer (BC).
Major finding: The median durations of progression-free survival were 5.7 months and 9.4 months in patients with and without prior exposure to fluoropyrimidine therapy, respectively. Neutropenia (81.8%), fatigue (29.7%), anorexia (25.7%), and nausea (25.7%) were the most common all-grade treatment-related adverse events.
Study details: Findings are from a phase 2 study including 74 patients with metastatic BC with or without prior exposure to fluoropyrimidine therapy who received FTD/TPI.
Disclosures: This study was funded by a grant from the National Medical Research Council, Singapore. Some authors declared receiving research funding, honoraria, consulting fees, or travel support from or having other ties with various sources.
Source: Lim JSJ et al. Phase II study of trifluridine/tipiracil (FTD/TPI) in metastatic breast cancers with or without prior exposure to fluoropyrimidines. Eur J Cancer. 2023;113311 (Aug 25). doi: 10.1016/j.ejca.2023.113311
Key clinical point: Trifluridine/tipiracil (FTD/TPI) showed promising anti-tumor activity with a manageable safety profile regardless of prior exposure to fluoropyrimidine therapy in patients with metastatic breast cancer (BC).
Major finding: The median durations of progression-free survival were 5.7 months and 9.4 months in patients with and without prior exposure to fluoropyrimidine therapy, respectively. Neutropenia (81.8%), fatigue (29.7%), anorexia (25.7%), and nausea (25.7%) were the most common all-grade treatment-related adverse events.
Study details: Findings are from a phase 2 study including 74 patients with metastatic BC with or without prior exposure to fluoropyrimidine therapy who received FTD/TPI.
Disclosures: This study was funded by a grant from the National Medical Research Council, Singapore. Some authors declared receiving research funding, honoraria, consulting fees, or travel support from or having other ties with various sources.
Source: Lim JSJ et al. Phase II study of trifluridine/tipiracil (FTD/TPI) in metastatic breast cancers with or without prior exposure to fluoropyrimidines. Eur J Cancer. 2023;113311 (Aug 25). doi: 10.1016/j.ejca.2023.113311
Giredestrant shows promising outcomes in HR+ /HER2− BC in phase 2 study
Key clinical point: Giredestrant demonstrated stronger anti-proliferative activity than anastrozole and was well-tolerated in patients with estrogen receptor-positive (ER+ ), human epidermal growth factor receptor 2-negative (HER2−), untreated early breast cancer (BC).
Major finding: At week 2, giredestrant vs anastrozole had a stronger anti-proliferative effect as indicated by greater relative geometric mean reduction of Ki67 scores (−75% vs −67%; P = .043). Neutropenia (26% and 27%, respectively) and decreased neutrophil count (15% and 15%, respectively) were the most common grade 3-4 adverse events observed in the giredestrant + palbociclib and anastrozole + palbociclib treatment arms.
Study details: Findings are from the phase 2 coopERA Breast Cancer trial including 221 postmenopausal patients with clinical T stage (cT)1c to cT4a-c, ER+ /HER2− early BC who were randomly assigned to receive giredestrant or anastrozole in combination with palbociclib.
Disclosures: This study was funded by F Hoffmann-La Roche. Seven authors declared being employees or stockholders of F Hoffmann-La Roche, and the other authors declared ties with various sources.
Source: Hurvitz SA et al on behalf of thecoopERA Breast Cancer study group. Neoadjuvant palbociclib plus either giredestrant or anastrozole in oestrogen receptor-positive, HER2-negative, early breast cancer (coopERA Breast Cancer): An open-label, randomised, controlled, phase 2 study. Lancet Oncol. 2023;24(9):1029-1041 (Aug 29). doi: 10.1016/S1470-2045(23)00268-1
Key clinical point: Giredestrant demonstrated stronger anti-proliferative activity than anastrozole and was well-tolerated in patients with estrogen receptor-positive (ER+ ), human epidermal growth factor receptor 2-negative (HER2−), untreated early breast cancer (BC).
Major finding: At week 2, giredestrant vs anastrozole had a stronger anti-proliferative effect as indicated by greater relative geometric mean reduction of Ki67 scores (−75% vs −67%; P = .043). Neutropenia (26% and 27%, respectively) and decreased neutrophil count (15% and 15%, respectively) were the most common grade 3-4 adverse events observed in the giredestrant + palbociclib and anastrozole + palbociclib treatment arms.
Study details: Findings are from the phase 2 coopERA Breast Cancer trial including 221 postmenopausal patients with clinical T stage (cT)1c to cT4a-c, ER+ /HER2− early BC who were randomly assigned to receive giredestrant or anastrozole in combination with palbociclib.
Disclosures: This study was funded by F Hoffmann-La Roche. Seven authors declared being employees or stockholders of F Hoffmann-La Roche, and the other authors declared ties with various sources.
Source: Hurvitz SA et al on behalf of thecoopERA Breast Cancer study group. Neoadjuvant palbociclib plus either giredestrant or anastrozole in oestrogen receptor-positive, HER2-negative, early breast cancer (coopERA Breast Cancer): An open-label, randomised, controlled, phase 2 study. Lancet Oncol. 2023;24(9):1029-1041 (Aug 29). doi: 10.1016/S1470-2045(23)00268-1
Key clinical point: Giredestrant demonstrated stronger anti-proliferative activity than anastrozole and was well-tolerated in patients with estrogen receptor-positive (ER+ ), human epidermal growth factor receptor 2-negative (HER2−), untreated early breast cancer (BC).
Major finding: At week 2, giredestrant vs anastrozole had a stronger anti-proliferative effect as indicated by greater relative geometric mean reduction of Ki67 scores (−75% vs −67%; P = .043). Neutropenia (26% and 27%, respectively) and decreased neutrophil count (15% and 15%, respectively) were the most common grade 3-4 adverse events observed in the giredestrant + palbociclib and anastrozole + palbociclib treatment arms.
Study details: Findings are from the phase 2 coopERA Breast Cancer trial including 221 postmenopausal patients with clinical T stage (cT)1c to cT4a-c, ER+ /HER2− early BC who were randomly assigned to receive giredestrant or anastrozole in combination with palbociclib.
Disclosures: This study was funded by F Hoffmann-La Roche. Seven authors declared being employees or stockholders of F Hoffmann-La Roche, and the other authors declared ties with various sources.
Source: Hurvitz SA et al on behalf of thecoopERA Breast Cancer study group. Neoadjuvant palbociclib plus either giredestrant or anastrozole in oestrogen receptor-positive, HER2-negative, early breast cancer (coopERA Breast Cancer): An open-label, randomised, controlled, phase 2 study. Lancet Oncol. 2023;24(9):1029-1041 (Aug 29). doi: 10.1016/S1470-2045(23)00268-1
Luminal A BC patients can skip radiotherapy after breast-conserving surgery
Key clinical point: The incidence rate of local recurrence was low even after omitting radiotherapy in women with luminal A breast cancer (BC) age ≥55 years who underwent breast-conserving surgery (BCS) followed by endocrine therapy.
Major finding: At 5 years, the cumulative incidence of local recurrence was low (2.3%; 95% CI 1.2%-4.1%), with 1.9% of patients (90% CI 1.1%-3.2%) reporting contralateral BC recurrences and 2.7% of patients (90% CI 1.6%-4.1%) reporting recurrences of any type.
Study details: This prospective cohort study included 500 women with T1N0 (tumor size < 2 cm and node negative) luminal A BC age ≥ 55 years who had undergone BCS followed by adjuvant endocrine therapy.
Disclosures: This study was supported by the Canadian Cancer Society and Canadian Breast Cancer Foundation. Some authors declared serving as consultants or members of data safety and monitoring boards or having ties with various sources.
Source: Whelan TJ et al for the LUMINA Study Investigators. Omitting radiotherapy after breast-conserving surgery in luminal A breast cancer. N Engl J Med. 2023;389(7):612-619 (Aug 17). doi: 10.1056/NEJMoa2302344
Key clinical point: The incidence rate of local recurrence was low even after omitting radiotherapy in women with luminal A breast cancer (BC) age ≥55 years who underwent breast-conserving surgery (BCS) followed by endocrine therapy.
Major finding: At 5 years, the cumulative incidence of local recurrence was low (2.3%; 95% CI 1.2%-4.1%), with 1.9% of patients (90% CI 1.1%-3.2%) reporting contralateral BC recurrences and 2.7% of patients (90% CI 1.6%-4.1%) reporting recurrences of any type.
Study details: This prospective cohort study included 500 women with T1N0 (tumor size < 2 cm and node negative) luminal A BC age ≥ 55 years who had undergone BCS followed by adjuvant endocrine therapy.
Disclosures: This study was supported by the Canadian Cancer Society and Canadian Breast Cancer Foundation. Some authors declared serving as consultants or members of data safety and monitoring boards or having ties with various sources.
Source: Whelan TJ et al for the LUMINA Study Investigators. Omitting radiotherapy after breast-conserving surgery in luminal A breast cancer. N Engl J Med. 2023;389(7):612-619 (Aug 17). doi: 10.1056/NEJMoa2302344
Key clinical point: The incidence rate of local recurrence was low even after omitting radiotherapy in women with luminal A breast cancer (BC) age ≥55 years who underwent breast-conserving surgery (BCS) followed by endocrine therapy.
Major finding: At 5 years, the cumulative incidence of local recurrence was low (2.3%; 95% CI 1.2%-4.1%), with 1.9% of patients (90% CI 1.1%-3.2%) reporting contralateral BC recurrences and 2.7% of patients (90% CI 1.6%-4.1%) reporting recurrences of any type.
Study details: This prospective cohort study included 500 women with T1N0 (tumor size < 2 cm and node negative) luminal A BC age ≥ 55 years who had undergone BCS followed by adjuvant endocrine therapy.
Disclosures: This study was supported by the Canadian Cancer Society and Canadian Breast Cancer Foundation. Some authors declared serving as consultants or members of data safety and monitoring boards or having ties with various sources.
Source: Whelan TJ et al for the LUMINA Study Investigators. Omitting radiotherapy after breast-conserving surgery in luminal A breast cancer. N Engl J Med. 2023;389(7):612-619 (Aug 17). doi: 10.1056/NEJMoa2302344
Role of Prophylactic Cranial Irradiation in Small Cell Carcinoma of Urinary Bladder: Case Report and Literature Review
INTRODUCTION
Urinary bladder is an extremely rare site of extrapulmonary small cell cancer (EPSCC). Unlike small cell lung cancer (SCLC), there is no clear guideline for prophylactic cranial irradiation (PCI) for EPSCC. In this case report and literature review, we discuss small cell cancer of urinary bladder (SCCUB) and the role of PCI in SCCUB.
CASE PRESENTATION
A 74-year-old male presented with gross hematuria and an unremarkable physical examination. CT showed 1.7 cm right anterolateral bladder wall thickening. Cystoscopy revealed a 2-3 cm high-grade bladder lesion. Pathology from transurethral resection of the tumor was consistent with T1N0M0 small cell carcinoma. MRI brain and FDG-PET showed no extravesical disease. Patient received four cycles of neoadjuvant carboplatin/etoposide per his preference as he wanted to protect his hearing due to his profession followed by radical cystoprostatectomy. Post-op pathology showed clear margins. We decided to forego PCI in favor of interval surveillance with MRI and follow- up images remain negative for distant metastases.
DISCUSSION
EPSCC accounts for 2.5-5% of all SCC, very rare in male genitourinary tract. Treatment approach is derived from SCLC, guided by extent of disease and patient’s functional status. Role of PCI in EPSCC has not been clearly described, and even less evidence is available for SCCUB. From a review of eleven studies in PubMed for the role of PCI in SCCUB or EPSCC, we found that SCCUB has lower incidence of brain metastases than SCLC. One study suggested that SCCUB arises from totipotent cells in the submucosa, unlike Kulchitsky cell origin of SCLC. This difference might explain the difference in their metastatic behavior. With this background, PCI is not routinely recommended for limited- stage SCCUB. There might still be a role for PCI in extensive SCCUB with high metastatic burden. More studies are needed to update the guidelines for the role of PCI for these tumors.
CONCLUSIONS
Per this literature review, PCI is not routinely recommended for SCCUB, likely due to different cells of origin compared to SCLC. Future studies should focus on characterizing differences in their metastatic behavior and updating guidelines for PCI for SCCUB.
INTRODUCTION
Urinary bladder is an extremely rare site of extrapulmonary small cell cancer (EPSCC). Unlike small cell lung cancer (SCLC), there is no clear guideline for prophylactic cranial irradiation (PCI) for EPSCC. In this case report and literature review, we discuss small cell cancer of urinary bladder (SCCUB) and the role of PCI in SCCUB.
CASE PRESENTATION
A 74-year-old male presented with gross hematuria and an unremarkable physical examination. CT showed 1.7 cm right anterolateral bladder wall thickening. Cystoscopy revealed a 2-3 cm high-grade bladder lesion. Pathology from transurethral resection of the tumor was consistent with T1N0M0 small cell carcinoma. MRI brain and FDG-PET showed no extravesical disease. Patient received four cycles of neoadjuvant carboplatin/etoposide per his preference as he wanted to protect his hearing due to his profession followed by radical cystoprostatectomy. Post-op pathology showed clear margins. We decided to forego PCI in favor of interval surveillance with MRI and follow- up images remain negative for distant metastases.
DISCUSSION
EPSCC accounts for 2.5-5% of all SCC, very rare in male genitourinary tract. Treatment approach is derived from SCLC, guided by extent of disease and patient’s functional status. Role of PCI in EPSCC has not been clearly described, and even less evidence is available for SCCUB. From a review of eleven studies in PubMed for the role of PCI in SCCUB or EPSCC, we found that SCCUB has lower incidence of brain metastases than SCLC. One study suggested that SCCUB arises from totipotent cells in the submucosa, unlike Kulchitsky cell origin of SCLC. This difference might explain the difference in their metastatic behavior. With this background, PCI is not routinely recommended for limited- stage SCCUB. There might still be a role for PCI in extensive SCCUB with high metastatic burden. More studies are needed to update the guidelines for the role of PCI for these tumors.
CONCLUSIONS
Per this literature review, PCI is not routinely recommended for SCCUB, likely due to different cells of origin compared to SCLC. Future studies should focus on characterizing differences in their metastatic behavior and updating guidelines for PCI for SCCUB.
INTRODUCTION
Urinary bladder is an extremely rare site of extrapulmonary small cell cancer (EPSCC). Unlike small cell lung cancer (SCLC), there is no clear guideline for prophylactic cranial irradiation (PCI) for EPSCC. In this case report and literature review, we discuss small cell cancer of urinary bladder (SCCUB) and the role of PCI in SCCUB.
CASE PRESENTATION
A 74-year-old male presented with gross hematuria and an unremarkable physical examination. CT showed 1.7 cm right anterolateral bladder wall thickening. Cystoscopy revealed a 2-3 cm high-grade bladder lesion. Pathology from transurethral resection of the tumor was consistent with T1N0M0 small cell carcinoma. MRI brain and FDG-PET showed no extravesical disease. Patient received four cycles of neoadjuvant carboplatin/etoposide per his preference as he wanted to protect his hearing due to his profession followed by radical cystoprostatectomy. Post-op pathology showed clear margins. We decided to forego PCI in favor of interval surveillance with MRI and follow- up images remain negative for distant metastases.
DISCUSSION
EPSCC accounts for 2.5-5% of all SCC, very rare in male genitourinary tract. Treatment approach is derived from SCLC, guided by extent of disease and patient’s functional status. Role of PCI in EPSCC has not been clearly described, and even less evidence is available for SCCUB. From a review of eleven studies in PubMed for the role of PCI in SCCUB or EPSCC, we found that SCCUB has lower incidence of brain metastases than SCLC. One study suggested that SCCUB arises from totipotent cells in the submucosa, unlike Kulchitsky cell origin of SCLC. This difference might explain the difference in their metastatic behavior. With this background, PCI is not routinely recommended for limited- stage SCCUB. There might still be a role for PCI in extensive SCCUB with high metastatic burden. More studies are needed to update the guidelines for the role of PCI for these tumors.
CONCLUSIONS
Per this literature review, PCI is not routinely recommended for SCCUB, likely due to different cells of origin compared to SCLC. Future studies should focus on characterizing differences in their metastatic behavior and updating guidelines for PCI for SCCUB.
Nonhealing postsurgical scalp ulcers
Two shave biopsies were taken, 1 in the center of a previous SCC site with hyperkeratosis, the other in a site not previously affected by SCC but with the physical features of a pustule. Biopsy results from both sites were consistent with erosive pustular dermatosis, an unusual inflammatory disorder that mimics SCC.
Erosive pustular dermatosis of the scalp is an uncommon dermatitis that usually affects older women but may appear in men and women of all ages. It can mimic many other conditions that can affect the scalp, including seborrheic dermatitis, psoriasis, actinic keratosis, and SCC.
The exact causative mechanism is not understood, and cases may develop spontaneously. Rough papules, pustules, crusts, and ulcers develop and (apart from the pustules) share many features of actinic keratoses, SCCs, and field cancerization. The presence of pustules helps point to the diagnosis.
Triggers include previous surgery or physical trauma, burns, skin or hair grafts, and treatment of actinic keratoses with imiquimod, 5-fluourouracil, or photodynamic therapy. Some autoimmune diseases (including Hashimoto thyroiditis, autoimmune hepatitis, and rheumatoid arthritis) have been linked to disease occurrence and severity.1
Treatment includes potent or super-potent topical steroids such as clobetasol 0.05% ointment. Topical tacrolimus 0.1% ointment and calcipotriene 0.005% cream have been reported as steroid alternatives. Paradoxically, photodynamic therapy, while associated with triggering disease, has also been used therapeutically. Systemic immunomodulators such as cyclosporine 3 mg/kg/d or prednisone 0.5 to 1 mg/kg/d may be needed in severe cases. Antibiotics including topical dapsone 5% gel, systemic dapsone from 50 mg bid to tid, and doxycycline have been helpful due, in part, to their immunomodulatory effects.1,2
This patient was told to apply topical triamcinolone 0.1% ointment around and over ulcers and pustules and to take doxycycline 100 mg twice daily. The patient cleared well after 6 weeks. He continued to apply topical triamcinolone every few days as maintenance therapy.
He had some mild recurrence after discontinuing all topical and oral therapy, so he currently is being maintained on topical clobetasol 0.05% ointment every other day. He comes in for follow-up appointments every 3 months to monitor for control of the erosive pustular dermatosis of the scalp and for skin cancer surveillance.
Photos and text for Photo Rounds Friday courtesy of Jonathan Karnes, MD (copyright retained). Dr. Karnes is the medical director of MDFMR Dermatology Services, Augusta, ME
1. Karanfilian KM, Wassef C. Erosive pustular dermatosis of the scalp: causes and treatments. Int J Dermatol. 2021;60:25-32. doi: 10.1111/ijd.14955
2. Sasaki R, Asano Y, Fujimura T. A pediatric case of corticosteroid-resistant erosive pustular dermatosis of scalp-like alopecia treated successfully with oral indomethacin, doxycycline, and topical tacrolimus. J Dermatol. 2022;49: e299-e300. doi: 10.1111/1346-8138.16425
Two shave biopsies were taken, 1 in the center of a previous SCC site with hyperkeratosis, the other in a site not previously affected by SCC but with the physical features of a pustule. Biopsy results from both sites were consistent with erosive pustular dermatosis, an unusual inflammatory disorder that mimics SCC.
Erosive pustular dermatosis of the scalp is an uncommon dermatitis that usually affects older women but may appear in men and women of all ages. It can mimic many other conditions that can affect the scalp, including seborrheic dermatitis, psoriasis, actinic keratosis, and SCC.
The exact causative mechanism is not understood, and cases may develop spontaneously. Rough papules, pustules, crusts, and ulcers develop and (apart from the pustules) share many features of actinic keratoses, SCCs, and field cancerization. The presence of pustules helps point to the diagnosis.
Triggers include previous surgery or physical trauma, burns, skin or hair grafts, and treatment of actinic keratoses with imiquimod, 5-fluourouracil, or photodynamic therapy. Some autoimmune diseases (including Hashimoto thyroiditis, autoimmune hepatitis, and rheumatoid arthritis) have been linked to disease occurrence and severity.1
Treatment includes potent or super-potent topical steroids such as clobetasol 0.05% ointment. Topical tacrolimus 0.1% ointment and calcipotriene 0.005% cream have been reported as steroid alternatives. Paradoxically, photodynamic therapy, while associated with triggering disease, has also been used therapeutically. Systemic immunomodulators such as cyclosporine 3 mg/kg/d or prednisone 0.5 to 1 mg/kg/d may be needed in severe cases. Antibiotics including topical dapsone 5% gel, systemic dapsone from 50 mg bid to tid, and doxycycline have been helpful due, in part, to their immunomodulatory effects.1,2
This patient was told to apply topical triamcinolone 0.1% ointment around and over ulcers and pustules and to take doxycycline 100 mg twice daily. The patient cleared well after 6 weeks. He continued to apply topical triamcinolone every few days as maintenance therapy.
He had some mild recurrence after discontinuing all topical and oral therapy, so he currently is being maintained on topical clobetasol 0.05% ointment every other day. He comes in for follow-up appointments every 3 months to monitor for control of the erosive pustular dermatosis of the scalp and for skin cancer surveillance.
Photos and text for Photo Rounds Friday courtesy of Jonathan Karnes, MD (copyright retained). Dr. Karnes is the medical director of MDFMR Dermatology Services, Augusta, ME
Two shave biopsies were taken, 1 in the center of a previous SCC site with hyperkeratosis, the other in a site not previously affected by SCC but with the physical features of a pustule. Biopsy results from both sites were consistent with erosive pustular dermatosis, an unusual inflammatory disorder that mimics SCC.
Erosive pustular dermatosis of the scalp is an uncommon dermatitis that usually affects older women but may appear in men and women of all ages. It can mimic many other conditions that can affect the scalp, including seborrheic dermatitis, psoriasis, actinic keratosis, and SCC.
The exact causative mechanism is not understood, and cases may develop spontaneously. Rough papules, pustules, crusts, and ulcers develop and (apart from the pustules) share many features of actinic keratoses, SCCs, and field cancerization. The presence of pustules helps point to the diagnosis.
Triggers include previous surgery or physical trauma, burns, skin or hair grafts, and treatment of actinic keratoses with imiquimod, 5-fluourouracil, or photodynamic therapy. Some autoimmune diseases (including Hashimoto thyroiditis, autoimmune hepatitis, and rheumatoid arthritis) have been linked to disease occurrence and severity.1
Treatment includes potent or super-potent topical steroids such as clobetasol 0.05% ointment. Topical tacrolimus 0.1% ointment and calcipotriene 0.005% cream have been reported as steroid alternatives. Paradoxically, photodynamic therapy, while associated with triggering disease, has also been used therapeutically. Systemic immunomodulators such as cyclosporine 3 mg/kg/d or prednisone 0.5 to 1 mg/kg/d may be needed in severe cases. Antibiotics including topical dapsone 5% gel, systemic dapsone from 50 mg bid to tid, and doxycycline have been helpful due, in part, to their immunomodulatory effects.1,2
This patient was told to apply topical triamcinolone 0.1% ointment around and over ulcers and pustules and to take doxycycline 100 mg twice daily. The patient cleared well after 6 weeks. He continued to apply topical triamcinolone every few days as maintenance therapy.
He had some mild recurrence after discontinuing all topical and oral therapy, so he currently is being maintained on topical clobetasol 0.05% ointment every other day. He comes in for follow-up appointments every 3 months to monitor for control of the erosive pustular dermatosis of the scalp and for skin cancer surveillance.
Photos and text for Photo Rounds Friday courtesy of Jonathan Karnes, MD (copyright retained). Dr. Karnes is the medical director of MDFMR Dermatology Services, Augusta, ME
1. Karanfilian KM, Wassef C. Erosive pustular dermatosis of the scalp: causes and treatments. Int J Dermatol. 2021;60:25-32. doi: 10.1111/ijd.14955
2. Sasaki R, Asano Y, Fujimura T. A pediatric case of corticosteroid-resistant erosive pustular dermatosis of scalp-like alopecia treated successfully with oral indomethacin, doxycycline, and topical tacrolimus. J Dermatol. 2022;49: e299-e300. doi: 10.1111/1346-8138.16425
1. Karanfilian KM, Wassef C. Erosive pustular dermatosis of the scalp: causes and treatments. Int J Dermatol. 2021;60:25-32. doi: 10.1111/ijd.14955
2. Sasaki R, Asano Y, Fujimura T. A pediatric case of corticosteroid-resistant erosive pustular dermatosis of scalp-like alopecia treated successfully with oral indomethacin, doxycycline, and topical tacrolimus. J Dermatol. 2022;49: e299-e300. doi: 10.1111/1346-8138.16425
Olfactory Hallucinations Following COVID-19 Vaccination
The rapid development of multiple vaccines for COVID-19 significantly contributed to reducing the morbidity and mortality associated with COVID-19 infection.1 The vaccination campaign against COVID-19 started in December 2020 within the US Department of Veterans Affairs (VA) health care system with the Pfizer-BioNTech and Moderna COVID-19 mRNA vaccines followed by the Johnson & Johnson (J&J) vaccine in March 2021.2,3
Because of the importance of maintaining a safe vaccination campaign, surveillance reports documenting cases of malignant or benign adverse effects (AEs) are fundamental to generate awareness and accurate knowledge on these newly developed vaccines. Here we report the case of a veteran who developed olfactory hallucinations following the administration of the J&J COVID-19 vaccine.
Case Presentation
A 39-year-old veteran with a history of tension-type headaches presented to the neurology clinic with concern of a burning smell sensation in the absence of an identifiable source. He first noticed this symptom approximately 3 weeks after he received the J&J COVID-19 vaccine about 4 months prior. At the symptom’s first occurrence, he underwent a nasal swab antigen COVID-19 test, which was negative. Initially, symptoms would occur daily lasting about 1 hour. Thereafter, they started to decrease in duration, frequency, and intensity, and about 11 months postvaccination, milder episodes were occurring 1 to 2 times weekly. These episodes lasted nearly 2 years (21 months postvaccination). They happened randomly during the day and were not associated with any other symptoms. Specifically, there were no headaches, loss of consciousness, abnormal movements, nausea, vomiting, photophobia or phonophobia, or alteration of consciousness, such as confusion or drowsiness during or after the events. Additionally, there were no clear triggers the veteran could identify. The veteran did not sustain any head injuries or exposure to toxic odors before the onset of symptoms.
At the time of his presentation to the clinic, both his general and neurological examinations were unremarkable.
Discussion
It has been previously observed that infection with COVID-19 can lead to the loss of taste and smell, but only less commonly olfactory hallucination.4 The pathophysiology of olfactory hallucinations following COVID-19 infection is unknown, but several mechanisms have been proposed. These include obstruction of the olfactory cleft; infection of the sustentacular supporting cells, which express angiotensin‐converting enzyme 2 (ACE‐2); injury to olfactory sensory cells via neuropilin‐1 receptors (NRP1); and injury to the olfactory bulb.5
The case we present represents the only report of phantosmia following a J&J COVID-19 vaccination. Phantosmia, featured by a burning or smoke odor, has been reported prior in a case of a 57-year-old woman following the administration of the Pfizer-BioNTech mRNA vaccine.6 Similar to our case, symptoms were not associated with a concurrent COVID-19 infection ruled out via a COVID-19 polymerase chain reaction test. For the Pfizer-BioNTech phantosmia case, a 3 Tesla (T) brain MRI showed left greater than right olfactory bulb and tract gadolinium enhancement on T1-weighted postcontrast images. On axial T2-weighted fluid-attenuated inversion recovery images, hyperintensity along the left olfactory bulb and bilateral olfactory tracts was noted and interpreted as edema. On sagittal thin sections of T2-weighted images, the olfactory nerve filia were thickened and clumped.6 On the contrary, in the case we present, a brain MRI obtained with a 1.5 T magnet showed no abnormalities. It is possible that a high-resolution scan targeting the olfactory bulb could have disclosed pathological changes. At the time when the veteran presented to the neurology clinic, symptoms were already improving, and repeat MRI was deferred as it would not have changed the clinical management.
Konstantinidis and colleagues reported hyposmia in 2 patients following Pfizer-BioNTech COVID-19 vaccination.5 Both patients, 42- and 39-year-old women, experienced hyposmia following their second dose of the vaccine with symptom onset 3 and 5 days after vaccination, respectively. The first patient reported improvement of symptoms after 1 week, while the second patient participated in olfactory training and experienced only partial recovery after 1 month. Multiple studies have reported cranial nerve involvement secondary to other COVID-19 vaccines, including olfactory dysfunction, optic neuritis, acute abducens nerve palsy, Bell palsy, tinnitus, and cochleopathy.7
There are no previous reports of phantosmia following the J&J COVID-19 vaccine. In our case, reported symptoms were mild, although they persisted for nearly 2 years following vaccination.
In the evaluation of this veteran, although the timing between symptom onset and vaccination was indicative of a possible link between the 2, other etiologies of phantosmia were ruled out. Isolated olfactory hallucination is most associated with temporal lobe epilepsy, which is the most common form of epilepsy to present in adulthood. However, given the absence of other symptoms suggestive of epilepsy and the duration of the episodes (approximately 1 hour), the clinical suspicion was low. This was reinforced by the EEG that showed no abnormalities in the temporal region. Notwithstanding these considerations, one must keep in mind that no episodes of phantosmia occurred during the EEG recording, the correlates of which are the gold standard to rule out a diagnosis of epilepsy.
A normal brain MRI argued against possible structural abnormalities leading to these symptoms. Thus, the origin of these symptoms remains unknown.
Conclusions
The emergency approval and use of vaccines against COVID-19 was a major victory for public health in 2021. However, given the rapid rollout of these vaccines, the medical community is responsible for reporting adverse effects as they are observed. The authors believe that the clinical events featuring the J&J COVID-19 vaccine in this veteran should not discourage the use of the COVID-19 vaccine. However, sharing the clinical outcome of this veteran is relevant to inform the community regarding this rare and benign possible adverse effect of the J&J COVID-19 vaccine.
Acknowledgments
This material is the result of work supported with resources and the use of facilities at the Tennessee Valley Veteran Healthcare System (Nashville). The authors thank Dr. Martin Gallagher (Tennessee Valley Veteran Healthcare System) for providing clinical expertise with electroencephalogram interpretation.
1. Xu S, Huang R, Sy LS, et al. COVID-19 vaccination and non-COVID-19 mortality risk - seven integrated health care organizations, United States, December 14, 2020-July 31, 2021. MMWR Morb Mortal Wkly Rep. 2021;70(43):1520-1524. Published 2021 Oct 29. doi:10.15585/mmwr.mm7043e2
2. Der-Martirosian C, Steers WN, Northcraft H, Chu K, Dobalian A. Vaccinating veterans for COVID-19 at the U.S. Department of Veterans Affairs. Am J Prev Med. 2022;62(6):e317-e324. doi:10.1016/j.amepre.2021.12.016
3. Bagnato F, Wallin M. COVID-19 vaccine in veterans with multiple sclerosis: protect the vulnerable. Fed Pract. 2021;38(suppl 1):S28-S32. doi:10.12788/fp.0113
4. Işlek A, Balcı MK. Phantosmia with COVID-19 related olfactory dysfunction: report of nine cases. Indian J Otolaryngol Head Neck Surg. 2022;74(suppl 2):2891-2893. doi:10.1007/s12070-021-02505-z
5. Konstantinidis I, Tsakiropoulou E, Hähner A, de With K, Poulas K, Hummel T. Olfactory dysfunction after coronavirus disease 2019 (COVID-19) vaccination. Int Forum Allergy Rhinol. 2021;11(9):1399-1401. doi:10.1002/alr.22809
6. Keir G, Maria NI, Kirsch CFE. Unique imaging findings of neurologic phantosmia following Pfizer-BioNtech COVID-19 vaccination: a case report. Top Magn Reson Imaging. 2021;30(3):133-137. doi:10.1097/RMR.0000000000000287
7. Garg RK, Paliwal VK. Spectrum of neurological complications following COVID-19 vaccination. Neurol Sci. 2022;43(1):3-40. doi:10.1007/s10072-021-05662-9
The rapid development of multiple vaccines for COVID-19 significantly contributed to reducing the morbidity and mortality associated with COVID-19 infection.1 The vaccination campaign against COVID-19 started in December 2020 within the US Department of Veterans Affairs (VA) health care system with the Pfizer-BioNTech and Moderna COVID-19 mRNA vaccines followed by the Johnson & Johnson (J&J) vaccine in March 2021.2,3
Because of the importance of maintaining a safe vaccination campaign, surveillance reports documenting cases of malignant or benign adverse effects (AEs) are fundamental to generate awareness and accurate knowledge on these newly developed vaccines. Here we report the case of a veteran who developed olfactory hallucinations following the administration of the J&J COVID-19 vaccine.
Case Presentation
A 39-year-old veteran with a history of tension-type headaches presented to the neurology clinic with concern of a burning smell sensation in the absence of an identifiable source. He first noticed this symptom approximately 3 weeks after he received the J&J COVID-19 vaccine about 4 months prior. At the symptom’s first occurrence, he underwent a nasal swab antigen COVID-19 test, which was negative. Initially, symptoms would occur daily lasting about 1 hour. Thereafter, they started to decrease in duration, frequency, and intensity, and about 11 months postvaccination, milder episodes were occurring 1 to 2 times weekly. These episodes lasted nearly 2 years (21 months postvaccination). They happened randomly during the day and were not associated with any other symptoms. Specifically, there were no headaches, loss of consciousness, abnormal movements, nausea, vomiting, photophobia or phonophobia, or alteration of consciousness, such as confusion or drowsiness during or after the events. Additionally, there were no clear triggers the veteran could identify. The veteran did not sustain any head injuries or exposure to toxic odors before the onset of symptoms.
At the time of his presentation to the clinic, both his general and neurological examinations were unremarkable.
Discussion
It has been previously observed that infection with COVID-19 can lead to the loss of taste and smell, but only less commonly olfactory hallucination.4 The pathophysiology of olfactory hallucinations following COVID-19 infection is unknown, but several mechanisms have been proposed. These include obstruction of the olfactory cleft; infection of the sustentacular supporting cells, which express angiotensin‐converting enzyme 2 (ACE‐2); injury to olfactory sensory cells via neuropilin‐1 receptors (NRP1); and injury to the olfactory bulb.5
The case we present represents the only report of phantosmia following a J&J COVID-19 vaccination. Phantosmia, featured by a burning or smoke odor, has been reported prior in a case of a 57-year-old woman following the administration of the Pfizer-BioNTech mRNA vaccine.6 Similar to our case, symptoms were not associated with a concurrent COVID-19 infection ruled out via a COVID-19 polymerase chain reaction test. For the Pfizer-BioNTech phantosmia case, a 3 Tesla (T) brain MRI showed left greater than right olfactory bulb and tract gadolinium enhancement on T1-weighted postcontrast images. On axial T2-weighted fluid-attenuated inversion recovery images, hyperintensity along the left olfactory bulb and bilateral olfactory tracts was noted and interpreted as edema. On sagittal thin sections of T2-weighted images, the olfactory nerve filia were thickened and clumped.6 On the contrary, in the case we present, a brain MRI obtained with a 1.5 T magnet showed no abnormalities. It is possible that a high-resolution scan targeting the olfactory bulb could have disclosed pathological changes. At the time when the veteran presented to the neurology clinic, symptoms were already improving, and repeat MRI was deferred as it would not have changed the clinical management.
Konstantinidis and colleagues reported hyposmia in 2 patients following Pfizer-BioNTech COVID-19 vaccination.5 Both patients, 42- and 39-year-old women, experienced hyposmia following their second dose of the vaccine with symptom onset 3 and 5 days after vaccination, respectively. The first patient reported improvement of symptoms after 1 week, while the second patient participated in olfactory training and experienced only partial recovery after 1 month. Multiple studies have reported cranial nerve involvement secondary to other COVID-19 vaccines, including olfactory dysfunction, optic neuritis, acute abducens nerve palsy, Bell palsy, tinnitus, and cochleopathy.7
There are no previous reports of phantosmia following the J&J COVID-19 vaccine. In our case, reported symptoms were mild, although they persisted for nearly 2 years following vaccination.
In the evaluation of this veteran, although the timing between symptom onset and vaccination was indicative of a possible link between the 2, other etiologies of phantosmia were ruled out. Isolated olfactory hallucination is most associated with temporal lobe epilepsy, which is the most common form of epilepsy to present in adulthood. However, given the absence of other symptoms suggestive of epilepsy and the duration of the episodes (approximately 1 hour), the clinical suspicion was low. This was reinforced by the EEG that showed no abnormalities in the temporal region. Notwithstanding these considerations, one must keep in mind that no episodes of phantosmia occurred during the EEG recording, the correlates of which are the gold standard to rule out a diagnosis of epilepsy.
A normal brain MRI argued against possible structural abnormalities leading to these symptoms. Thus, the origin of these symptoms remains unknown.
Conclusions
The emergency approval and use of vaccines against COVID-19 was a major victory for public health in 2021. However, given the rapid rollout of these vaccines, the medical community is responsible for reporting adverse effects as they are observed. The authors believe that the clinical events featuring the J&J COVID-19 vaccine in this veteran should not discourage the use of the COVID-19 vaccine. However, sharing the clinical outcome of this veteran is relevant to inform the community regarding this rare and benign possible adverse effect of the J&J COVID-19 vaccine.
Acknowledgments
This material is the result of work supported with resources and the use of facilities at the Tennessee Valley Veteran Healthcare System (Nashville). The authors thank Dr. Martin Gallagher (Tennessee Valley Veteran Healthcare System) for providing clinical expertise with electroencephalogram interpretation.
The rapid development of multiple vaccines for COVID-19 significantly contributed to reducing the morbidity and mortality associated with COVID-19 infection.1 The vaccination campaign against COVID-19 started in December 2020 within the US Department of Veterans Affairs (VA) health care system with the Pfizer-BioNTech and Moderna COVID-19 mRNA vaccines followed by the Johnson & Johnson (J&J) vaccine in March 2021.2,3
Because of the importance of maintaining a safe vaccination campaign, surveillance reports documenting cases of malignant or benign adverse effects (AEs) are fundamental to generate awareness and accurate knowledge on these newly developed vaccines. Here we report the case of a veteran who developed olfactory hallucinations following the administration of the J&J COVID-19 vaccine.
Case Presentation
A 39-year-old veteran with a history of tension-type headaches presented to the neurology clinic with concern of a burning smell sensation in the absence of an identifiable source. He first noticed this symptom approximately 3 weeks after he received the J&J COVID-19 vaccine about 4 months prior. At the symptom’s first occurrence, he underwent a nasal swab antigen COVID-19 test, which was negative. Initially, symptoms would occur daily lasting about 1 hour. Thereafter, they started to decrease in duration, frequency, and intensity, and about 11 months postvaccination, milder episodes were occurring 1 to 2 times weekly. These episodes lasted nearly 2 years (21 months postvaccination). They happened randomly during the day and were not associated with any other symptoms. Specifically, there were no headaches, loss of consciousness, abnormal movements, nausea, vomiting, photophobia or phonophobia, or alteration of consciousness, such as confusion or drowsiness during or after the events. Additionally, there were no clear triggers the veteran could identify. The veteran did not sustain any head injuries or exposure to toxic odors before the onset of symptoms.
At the time of his presentation to the clinic, both his general and neurological examinations were unremarkable.
Discussion
It has been previously observed that infection with COVID-19 can lead to the loss of taste and smell, but only less commonly olfactory hallucination.4 The pathophysiology of olfactory hallucinations following COVID-19 infection is unknown, but several mechanisms have been proposed. These include obstruction of the olfactory cleft; infection of the sustentacular supporting cells, which express angiotensin‐converting enzyme 2 (ACE‐2); injury to olfactory sensory cells via neuropilin‐1 receptors (NRP1); and injury to the olfactory bulb.5
The case we present represents the only report of phantosmia following a J&J COVID-19 vaccination. Phantosmia, featured by a burning or smoke odor, has been reported prior in a case of a 57-year-old woman following the administration of the Pfizer-BioNTech mRNA vaccine.6 Similar to our case, symptoms were not associated with a concurrent COVID-19 infection ruled out via a COVID-19 polymerase chain reaction test. For the Pfizer-BioNTech phantosmia case, a 3 Tesla (T) brain MRI showed left greater than right olfactory bulb and tract gadolinium enhancement on T1-weighted postcontrast images. On axial T2-weighted fluid-attenuated inversion recovery images, hyperintensity along the left olfactory bulb and bilateral olfactory tracts was noted and interpreted as edema. On sagittal thin sections of T2-weighted images, the olfactory nerve filia were thickened and clumped.6 On the contrary, in the case we present, a brain MRI obtained with a 1.5 T magnet showed no abnormalities. It is possible that a high-resolution scan targeting the olfactory bulb could have disclosed pathological changes. At the time when the veteran presented to the neurology clinic, symptoms were already improving, and repeat MRI was deferred as it would not have changed the clinical management.
Konstantinidis and colleagues reported hyposmia in 2 patients following Pfizer-BioNTech COVID-19 vaccination.5 Both patients, 42- and 39-year-old women, experienced hyposmia following their second dose of the vaccine with symptom onset 3 and 5 days after vaccination, respectively. The first patient reported improvement of symptoms after 1 week, while the second patient participated in olfactory training and experienced only partial recovery after 1 month. Multiple studies have reported cranial nerve involvement secondary to other COVID-19 vaccines, including olfactory dysfunction, optic neuritis, acute abducens nerve palsy, Bell palsy, tinnitus, and cochleopathy.7
There are no previous reports of phantosmia following the J&J COVID-19 vaccine. In our case, reported symptoms were mild, although they persisted for nearly 2 years following vaccination.
In the evaluation of this veteran, although the timing between symptom onset and vaccination was indicative of a possible link between the 2, other etiologies of phantosmia were ruled out. Isolated olfactory hallucination is most associated with temporal lobe epilepsy, which is the most common form of epilepsy to present in adulthood. However, given the absence of other symptoms suggestive of epilepsy and the duration of the episodes (approximately 1 hour), the clinical suspicion was low. This was reinforced by the EEG that showed no abnormalities in the temporal region. Notwithstanding these considerations, one must keep in mind that no episodes of phantosmia occurred during the EEG recording, the correlates of which are the gold standard to rule out a diagnosis of epilepsy.
A normal brain MRI argued against possible structural abnormalities leading to these symptoms. Thus, the origin of these symptoms remains unknown.
Conclusions
The emergency approval and use of vaccines against COVID-19 was a major victory for public health in 2021. However, given the rapid rollout of these vaccines, the medical community is responsible for reporting adverse effects as they are observed. The authors believe that the clinical events featuring the J&J COVID-19 vaccine in this veteran should not discourage the use of the COVID-19 vaccine. However, sharing the clinical outcome of this veteran is relevant to inform the community regarding this rare and benign possible adverse effect of the J&J COVID-19 vaccine.
Acknowledgments
This material is the result of work supported with resources and the use of facilities at the Tennessee Valley Veteran Healthcare System (Nashville). The authors thank Dr. Martin Gallagher (Tennessee Valley Veteran Healthcare System) for providing clinical expertise with electroencephalogram interpretation.
1. Xu S, Huang R, Sy LS, et al. COVID-19 vaccination and non-COVID-19 mortality risk - seven integrated health care organizations, United States, December 14, 2020-July 31, 2021. MMWR Morb Mortal Wkly Rep. 2021;70(43):1520-1524. Published 2021 Oct 29. doi:10.15585/mmwr.mm7043e2
2. Der-Martirosian C, Steers WN, Northcraft H, Chu K, Dobalian A. Vaccinating veterans for COVID-19 at the U.S. Department of Veterans Affairs. Am J Prev Med. 2022;62(6):e317-e324. doi:10.1016/j.amepre.2021.12.016
3. Bagnato F, Wallin M. COVID-19 vaccine in veterans with multiple sclerosis: protect the vulnerable. Fed Pract. 2021;38(suppl 1):S28-S32. doi:10.12788/fp.0113
4. Işlek A, Balcı MK. Phantosmia with COVID-19 related olfactory dysfunction: report of nine cases. Indian J Otolaryngol Head Neck Surg. 2022;74(suppl 2):2891-2893. doi:10.1007/s12070-021-02505-z
5. Konstantinidis I, Tsakiropoulou E, Hähner A, de With K, Poulas K, Hummel T. Olfactory dysfunction after coronavirus disease 2019 (COVID-19) vaccination. Int Forum Allergy Rhinol. 2021;11(9):1399-1401. doi:10.1002/alr.22809
6. Keir G, Maria NI, Kirsch CFE. Unique imaging findings of neurologic phantosmia following Pfizer-BioNtech COVID-19 vaccination: a case report. Top Magn Reson Imaging. 2021;30(3):133-137. doi:10.1097/RMR.0000000000000287
7. Garg RK, Paliwal VK. Spectrum of neurological complications following COVID-19 vaccination. Neurol Sci. 2022;43(1):3-40. doi:10.1007/s10072-021-05662-9
1. Xu S, Huang R, Sy LS, et al. COVID-19 vaccination and non-COVID-19 mortality risk - seven integrated health care organizations, United States, December 14, 2020-July 31, 2021. MMWR Morb Mortal Wkly Rep. 2021;70(43):1520-1524. Published 2021 Oct 29. doi:10.15585/mmwr.mm7043e2
2. Der-Martirosian C, Steers WN, Northcraft H, Chu K, Dobalian A. Vaccinating veterans for COVID-19 at the U.S. Department of Veterans Affairs. Am J Prev Med. 2022;62(6):e317-e324. doi:10.1016/j.amepre.2021.12.016
3. Bagnato F, Wallin M. COVID-19 vaccine in veterans with multiple sclerosis: protect the vulnerable. Fed Pract. 2021;38(suppl 1):S28-S32. doi:10.12788/fp.0113
4. Işlek A, Balcı MK. Phantosmia with COVID-19 related olfactory dysfunction: report of nine cases. Indian J Otolaryngol Head Neck Surg. 2022;74(suppl 2):2891-2893. doi:10.1007/s12070-021-02505-z
5. Konstantinidis I, Tsakiropoulou E, Hähner A, de With K, Poulas K, Hummel T. Olfactory dysfunction after coronavirus disease 2019 (COVID-19) vaccination. Int Forum Allergy Rhinol. 2021;11(9):1399-1401. doi:10.1002/alr.22809
6. Keir G, Maria NI, Kirsch CFE. Unique imaging findings of neurologic phantosmia following Pfizer-BioNtech COVID-19 vaccination: a case report. Top Magn Reson Imaging. 2021;30(3):133-137. doi:10.1097/RMR.0000000000000287
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