Vimala Thalody

Background

Use of immune checkpoint inhibitors against advanced stage NSCLC has been associated with significant reduction in overall disease morbidity and mortality. However, despite the significant survival benefit, tumors invariably relapse. It is important to understand the pattern of progression and the progression free survival (PFS) to better predict disease outcomes and modify treatment approach.

Methods

We performed a retrospective review of 74 veterans with new diagnosis of stage IV NSCLC who received 2 or more cycles of immunotherapy with/without concurrent chemotherapy between 2015-2021 at the Stratton VA Medical Center. IRB approval was obtained. Fisher exact probability test and Kaplan-Meier estimators were used to analyze data with level of significance P < .05.

Results

Out of 74 patients, 38 patients were identified who received immunotherapy alone (Group A; n = 23, 60.5%) vs chemo-immunotherapy (Group B; n = 15, 39.5%). Baseline characteristics of Group A revealed median age 70 (IQR, 65-78), adenocarcinoma (n = 10, 43.4%), squamous cell carcinoma (n = 12, 52.1%), PD-L1 > 50% expression (n = 21, 91.3%), molecular testing positive for EGFR in 1 patient, otherwise negative for ROS, ALK, EGFR and BRAF mutations in all patients. Similarly, in Group B, median age 66 (IQR, 63-72), adenocarcinoma (n = 6, 40%), squamous cell carcinoma (n = 8, 53.3%), PD-L1 > 50% expression (n = 3, 20%), no mutations noted on molecular testing. Out of 38 patients, disease progression was noted in 19 patients, 10 in Group A (progression at initial site and new site n = 5, 50%) vs 9 in Group B (progression at initial site and new site, n = 6, 66.7%). Most common sites of progression included local and distant lymph nodes, brain, bone, and liver. Using the Kaplan-Meier analysis, median progression free survival (PFS) from start of immunotherapy till evidence of progression on imaging was 11 months in Group A and 7 months in Group B, P = .22. Our study recognized widespread metastases at the time of diagnosis (P = .03) as a possible factor affecting progression of diseases in Group A compared to Group B.

Conclusion

We conclude that although no statistically significant association was noted between the progression free survival between the two groups, the increased median PFS in immunotherapy only group is worth additional investigation. We recommend further large-scale studies to explore this association.

Background

Use of immune checkpoint inhibitors against advanced stage NSCLC has been associated with significant reduction in overall disease morbidity and mortality. However, despite the significant survival benefit, tumors invariably relapse. It is important to understand the pattern of progression and the progression free survival (PFS) to better predict disease outcomes and modify treatment approach.

Methods

We performed a retrospective review of 74 veterans with new diagnosis of stage IV NSCLC who received 2 or more cycles of immunotherapy with/without concurrent chemotherapy between 2015-2021 at the Stratton VA Medical Center. IRB approval was obtained. Fisher exact probability test and Kaplan-Meier estimators were used to analyze data with level of significance P < .05.

Results

Out of 74 patients, 38 patients were identified who received immunotherapy alone (Group A; n = 23, 60.5%) vs chemo-immunotherapy (Group B; n = 15, 39.5%). Baseline characteristics of Group A revealed median age 70 (IQR, 65-78), adenocarcinoma (n = 10, 43.4%), squamous cell carcinoma (n = 12, 52.1%), PD-L1 > 50% expression (n = 21, 91.3%), molecular testing positive for EGFR in 1 patient, otherwise negative for ROS, ALK, EGFR and BRAF mutations in all patients. Similarly, in Group B, median age 66 (IQR, 63-72), adenocarcinoma (n = 6, 40%), squamous cell carcinoma (n = 8, 53.3%), PD-L1 > 50% expression (n = 3, 20%), no mutations noted on molecular testing. Out of 38 patients, disease progression was noted in 19 patients, 10 in Group A (progression at initial site and new site n = 5, 50%) vs 9 in Group B (progression at initial site and new site, n = 6, 66.7%). Most common sites of progression included local and distant lymph nodes, brain, bone, and liver. Using the Kaplan-Meier analysis, median progression free survival (PFS) from start of immunotherapy till evidence of progression on imaging was 11 months in Group A and 7 months in Group B, P = .22. Our study recognized widespread metastases at the time of diagnosis (P = .03) as a possible factor affecting progression of diseases in Group A compared to Group B.

Conclusion

We conclude that although no statistically significant association was noted between the progression free survival between the two groups, the increased median PFS in immunotherapy only group is worth additional investigation. We recommend further large-scale studies to explore this association.

Background

Use of immune checkpoint inhibitors against advanced stage NSCLC has been associated with significant reduction in overall disease morbidity and mortality. However, despite the significant survival benefit, tumors invariably relapse. It is important to understand the pattern of progression and the progression free survival (PFS) to better predict disease outcomes and modify treatment approach.

Methods

We performed a retrospective review of 74 veterans with new diagnosis of stage IV NSCLC who received 2 or more cycles of immunotherapy with/without concurrent chemotherapy between 2015-2021 at the Stratton VA Medical Center. IRB approval was obtained. Fisher exact probability test and Kaplan-Meier estimators were used to analyze data with level of significance P < .05.

Results

Out of 74 patients, 38 patients were identified who received immunotherapy alone (Group A; n = 23, 60.5%) vs chemo-immunotherapy (Group B; n = 15, 39.5%). Baseline characteristics of Group A revealed median age 70 (IQR, 65-78), adenocarcinoma (n = 10, 43.4%), squamous cell carcinoma (n = 12, 52.1%), PD-L1 > 50% expression (n = 21, 91.3%), molecular testing positive for EGFR in 1 patient, otherwise negative for ROS, ALK, EGFR and BRAF mutations in all patients. Similarly, in Group B, median age 66 (IQR, 63-72), adenocarcinoma (n = 6, 40%), squamous cell carcinoma (n = 8, 53.3%), PD-L1 > 50% expression (n = 3, 20%), no mutations noted on molecular testing. Out of 38 patients, disease progression was noted in 19 patients, 10 in Group A (progression at initial site and new site n = 5, 50%) vs 9 in Group B (progression at initial site and new site, n = 6, 66.7%). Most common sites of progression included local and distant lymph nodes, brain, bone, and liver. Using the Kaplan-Meier analysis, median progression free survival (PFS) from start of immunotherapy till evidence of progression on imaging was 11 months in Group A and 7 months in Group B, P = .22. Our study recognized widespread metastases at the time of diagnosis (P = .03) as a possible factor affecting progression of diseases in Group A compared to Group B.

Conclusion

We conclude that although no statistically significant association was noted between the progression free survival between the two groups, the increased median PFS in immunotherapy only group is worth additional investigation. We recommend further large-scale studies to explore this association.

INTRODUCTION: American Society of Clinical Oncology (ASCO) has developed guidelines on the management of immune-related adverse events (irAEs) associated with immune checkpoint inhibitors (ICPIs). However, many irAEs are under-reported and the studies to investigate predictive factors are limited with variable results.

METHODS: A total of 66 patients who received ICPIs at Stratton VAMC Albany between January 2015 to December 2018 were studied. Computerized Patient Record System (CPRS) was used to do a retrospective chart review to identify irAEs and related parameters. IRB approval was obtained.

RESULTS: Sixty-three patients received PD-1 inhibitors (62 males). Our study included 39 patients with lung, 10 renal, 6 head and neck, 4 skin (melanoma), and 2 bladder cancers, and 1 metastatic cancer with unknown primary. Median age of patients with irAEs was 69.5 years versus 66.7 years for patients without irAEs. 23 (36.5%) patients experienced 28 irAEs. 45 patients received nivolumab, 18 (40%) of which had 21 irAEs. 17 got pembrolizumab and 5 (35.2%) had 7 irAEs. Majority of the irAEs were grade I (n=10, 35.7%) or grade II (n=11, 39.2%), while 6 (21.4%) grade III and only 1 (3.5%) grade IV irAE was observed. Median time to appearance of irAEs was 2 cycles. Immunotherapy was continued in 12, temporarily held in 7 and permanently discontinued only in 4 patients. No death was attributed to irAEs. Six patients developed diarrhea, 4 hepatitis, 6 skin rash, 5 thyroid issues and 3 pneumonitis. Rare irAEs included cardiac tamponade (grade IV), uveitis (grade II), central adrenal insufficiency and mild neutropenia in one patient each. 2 patients had pre-existing autoimmune conditions (rheumatoid arthritis and chronic dermatitis), both had transient flares though immunotherapy was continued. Of note, only 3 patients received PDL-1 inhibitors and 1 developed grade II polymyalgia rheumatica and hypothyroidism.

Using multivariate logistic regression, we found no significant association between irAEs and age, body mass index, derived neutrophil to lymphocyte ratio, chronic kidney disease or environmental/medical allergies.

CONCLUSIONS: ICPIs were generally well tolerated in our population, though prompt recognition of rare and severe irAEs is essential. Larger studies are needed to investigate the predictive risk factors for irAEs.

INTRODUCTION: American Society of Clinical Oncology (ASCO) has developed guidelines on the management of immune-related adverse events (irAEs) associated with immune checkpoint inhibitors (ICPIs). However, many irAEs are under-reported and the studies to investigate predictive factors are limited with variable results.

METHODS: A total of 66 patients who received ICPIs at Stratton VAMC Albany between January 2015 to December 2018 were studied. Computerized Patient Record System (CPRS) was used to do a retrospective chart review to identify irAEs and related parameters. IRB approval was obtained.

RESULTS: Sixty-three patients received PD-1 inhibitors (62 males). Our study included 39 patients with lung, 10 renal, 6 head and neck, 4 skin (melanoma), and 2 bladder cancers, and 1 metastatic cancer with unknown primary. Median age of patients with irAEs was 69.5 years versus 66.7 years for patients without irAEs. 23 (36.5%) patients experienced 28 irAEs. 45 patients received nivolumab, 18 (40%) of which had 21 irAEs. 17 got pembrolizumab and 5 (35.2%) had 7 irAEs. Majority of the irAEs were grade I (n=10, 35.7%) or grade II (n=11, 39.2%), while 6 (21.4%) grade III and only 1 (3.5%) grade IV irAE was observed. Median time to appearance of irAEs was 2 cycles. Immunotherapy was continued in 12, temporarily held in 7 and permanently discontinued only in 4 patients. No death was attributed to irAEs. Six patients developed diarrhea, 4 hepatitis, 6 skin rash, 5 thyroid issues and 3 pneumonitis. Rare irAEs included cardiac tamponade (grade IV), uveitis (grade II), central adrenal insufficiency and mild neutropenia in one patient each. 2 patients had pre-existing autoimmune conditions (rheumatoid arthritis and chronic dermatitis), both had transient flares though immunotherapy was continued. Of note, only 3 patients received PDL-1 inhibitors and 1 developed grade II polymyalgia rheumatica and hypothyroidism.

Using multivariate logistic regression, we found no significant association between irAEs and age, body mass index, derived neutrophil to lymphocyte ratio, chronic kidney disease or environmental/medical allergies.

CONCLUSIONS: ICPIs were generally well tolerated in our population, though prompt recognition of rare and severe irAEs is essential. Larger studies are needed to investigate the predictive risk factors for irAEs.

INTRODUCTION: American Society of Clinical Oncology (ASCO) has developed guidelines on the management of immune-related adverse events (irAEs) associated with immune checkpoint inhibitors (ICPIs). However, many irAEs are under-reported and the studies to investigate predictive factors are limited with variable results.

METHODS: A total of 66 patients who received ICPIs at Stratton VAMC Albany between January 2015 to December 2018 were studied. Computerized Patient Record System (CPRS) was used to do a retrospective chart review to identify irAEs and related parameters. IRB approval was obtained.

RESULTS: Sixty-three patients received PD-1 inhibitors (62 males). Our study included 39 patients with lung, 10 renal, 6 head and neck, 4 skin (melanoma), and 2 bladder cancers, and 1 metastatic cancer with unknown primary. Median age of patients with irAEs was 69.5 years versus 66.7 years for patients without irAEs. 23 (36.5%) patients experienced 28 irAEs. 45 patients received nivolumab, 18 (40%) of which had 21 irAEs. 17 got pembrolizumab and 5 (35.2%) had 7 irAEs. Majority of the irAEs were grade I (n=10, 35.7%) or grade II (n=11, 39.2%), while 6 (21.4%) grade III and only 1 (3.5%) grade IV irAE was observed. Median time to appearance of irAEs was 2 cycles. Immunotherapy was continued in 12, temporarily held in 7 and permanently discontinued only in 4 patients. No death was attributed to irAEs. Six patients developed diarrhea, 4 hepatitis, 6 skin rash, 5 thyroid issues and 3 pneumonitis. Rare irAEs included cardiac tamponade (grade IV), uveitis (grade II), central adrenal insufficiency and mild neutropenia in one patient each. 2 patients had pre-existing autoimmune conditions (rheumatoid arthritis and chronic dermatitis), both had transient flares though immunotherapy was continued. Of note, only 3 patients received PDL-1 inhibitors and 1 developed grade II polymyalgia rheumatica and hypothyroidism.

Using multivariate logistic regression, we found no significant association between irAEs and age, body mass index, derived neutrophil to lymphocyte ratio, chronic kidney disease or environmental/medical allergies.

CONCLUSIONS: ICPIs were generally well tolerated in our population, though prompt recognition of rare and severe irAEs is essential. Larger studies are needed to investigate the predictive risk factors for irAEs.

BACKGROUND: An 84-year-old male presented with a rapidly growing left breast mass associated with warmth, erythema, and serous discharge from left nipple for 2.5 months. Physical exam revealed ‘peau d’orange’ appearance of skin and a 3×7 cm, firm, irregular, fixed mass in left breast. Core needle biopsy of left breast revealed invasive ductal carcinoma and a computed tomography scan of chest showed multiple small pulmonary nodules. Patient was diagnosed with inflammatory breast carcinoma (Stage IV, cT4d cN1 cM1), ER/ PR positive, HER-2 positive. BRCA testing was negative. After a normal MUGA scan, patient was started on weekly paclitaxel and trastuzumab. After 4 cycles patient developed diarrhea and elected to stop paclitaxel. After 10 cycles of trastuzumab, patient developed signs of heart failure and a MUGA showed depressed left ventricular ejection fraction (LVEF). Trastuzumab was held and patient was started on tamoxifen. Patient had progression of primary mass into a fungating lesion and evidence of new pulmonary metastatic disease on tamoxifen. The primary lesion was treated with palliative radiation and after a subsequent MUGA scan showed normalization of LVEF; trastuzumab was resumed. Patient had stable disease on trastuzumab and continued to follow with oncology.

DISCUSSION: Male breast cancer is < 1% of all breast cancer but incidence is rising in the US. Risk factors include family history, BRCA2 > BRCA1, obesity, cirrhosis, and radiation exposure. Inflammatory breast cancer (IBC) is a rapidly progressive malignancy with a clinicopathological diagnosis. There are paucity of data of IBC in men due to rarity of the disease. Many patients initially are misdiagnosed with mastitis, unresponsive to antibiotics. At diagnosis, most patients have a higher age compared with females (by 5-10 years), and advanced stage, though have a similar prognosis by stage. Prognostic factors and treatment principles are same as females with multimodal approach of chemotherapy, radiation therapy, and hormone therapy.

CONCLUSIONS: IBC in men is very rare and awareness of its risk factors and presentation can lead to early diagnosis and better survival. Urgent referral to oncology is needed if index of suspicion is high. Further research is needed for defining best treatment modalities in elderly males.”

BACKGROUND: An 84-year-old male presented with a rapidly growing left breast mass associated with warmth, erythema, and serous discharge from left nipple for 2.5 months. Physical exam revealed ‘peau d’orange’ appearance of skin and a 3×7 cm, firm, irregular, fixed mass in left breast. Core needle biopsy of left breast revealed invasive ductal carcinoma and a computed tomography scan of chest showed multiple small pulmonary nodules. Patient was diagnosed with inflammatory breast carcinoma (Stage IV, cT4d cN1 cM1), ER/ PR positive, HER-2 positive. BRCA testing was negative. After a normal MUGA scan, patient was started on weekly paclitaxel and trastuzumab. After 4 cycles patient developed diarrhea and elected to stop paclitaxel. After 10 cycles of trastuzumab, patient developed signs of heart failure and a MUGA showed depressed left ventricular ejection fraction (LVEF). Trastuzumab was held and patient was started on tamoxifen. Patient had progression of primary mass into a fungating lesion and evidence of new pulmonary metastatic disease on tamoxifen. The primary lesion was treated with palliative radiation and after a subsequent MUGA scan showed normalization of LVEF; trastuzumab was resumed. Patient had stable disease on trastuzumab and continued to follow with oncology.

DISCUSSION: Male breast cancer is < 1% of all breast cancer but incidence is rising in the US. Risk factors include family history, BRCA2 > BRCA1, obesity, cirrhosis, and radiation exposure. Inflammatory breast cancer (IBC) is a rapidly progressive malignancy with a clinicopathological diagnosis. There are paucity of data of IBC in men due to rarity of the disease. Many patients initially are misdiagnosed with mastitis, unresponsive to antibiotics. At diagnosis, most patients have a higher age compared with females (by 5-10 years), and advanced stage, though have a similar prognosis by stage. Prognostic factors and treatment principles are same as females with multimodal approach of chemotherapy, radiation therapy, and hormone therapy.

CONCLUSIONS: IBC in men is very rare and awareness of its risk factors and presentation can lead to early diagnosis and better survival. Urgent referral to oncology is needed if index of suspicion is high. Further research is needed for defining best treatment modalities in elderly males.”

BACKGROUND: An 84-year-old male presented with a rapidly growing left breast mass associated with warmth, erythema, and serous discharge from left nipple for 2.5 months. Physical exam revealed ‘peau d’orange’ appearance of skin and a 3×7 cm, firm, irregular, fixed mass in left breast. Core needle biopsy of left breast revealed invasive ductal carcinoma and a computed tomography scan of chest showed multiple small pulmonary nodules. Patient was diagnosed with inflammatory breast carcinoma (Stage IV, cT4d cN1 cM1), ER/ PR positive, HER-2 positive. BRCA testing was negative. After a normal MUGA scan, patient was started on weekly paclitaxel and trastuzumab. After 4 cycles patient developed diarrhea and elected to stop paclitaxel. After 10 cycles of trastuzumab, patient developed signs of heart failure and a MUGA showed depressed left ventricular ejection fraction (LVEF). Trastuzumab was held and patient was started on tamoxifen. Patient had progression of primary mass into a fungating lesion and evidence of new pulmonary metastatic disease on tamoxifen. The primary lesion was treated with palliative radiation and after a subsequent MUGA scan showed normalization of LVEF; trastuzumab was resumed. Patient had stable disease on trastuzumab and continued to follow with oncology.

DISCUSSION: Male breast cancer is < 1% of all breast cancer but incidence is rising in the US. Risk factors include family history, BRCA2 > BRCA1, obesity, cirrhosis, and radiation exposure. Inflammatory breast cancer (IBC) is a rapidly progressive malignancy with a clinicopathological diagnosis. There are paucity of data of IBC in men due to rarity of the disease. Many patients initially are misdiagnosed with mastitis, unresponsive to antibiotics. At diagnosis, most patients have a higher age compared with females (by 5-10 years), and advanced stage, though have a similar prognosis by stage. Prognostic factors and treatment principles are same as females with multimodal approach of chemotherapy, radiation therapy, and hormone therapy.

CONCLUSIONS: IBC in men is very rare and awareness of its risk factors and presentation can lead to early diagnosis and better survival. Urgent referral to oncology is needed if index of suspicion is high. Further research is needed for defining best treatment modalities in elderly males.”