Comprehensive germline profiling of patients with breast cancer: initial experience from a Familial Cancer Clinic.

Introduction: Breast cancer is the most common cancer among Indian females. There is limited data on germline profiling of breast cancer patients from India. Objective: The objective of the current study was to analyse the frequency and spectrum of germline variant profiles and clinicopathological characteristics of breast cancer patients referred to our Familial Cancer Clinic (FCC). Materials and methods: It is a single-centre audit of patients with a confirmed diagnosis of breast carcinoma referred to our FCC from January 2017 to 2020. All patients underwent pretest counselling. Genetic testing was done by multigene panel testing by next-generation sequencing along with reflex multiplication ligation-dependent probe amplification for BRCA1 and 2. The variants were classified based on American College of Medical Genetics guidelines. Demographic and clinicopathological details were extracted from the case record files. Results: One hundred and fifty-five patients were referred to the FCC and underwent pretest counselling. A total of 99 (63.9%) patients underwent genetic testing. Among them, 62 patients (62/99 = 62.6%) had a germline variant. A pathogenic/likely pathogenic (P/LP) germline variant was identified in 41 (41.4%) of the patients who underwent testing. Additional variants of unknown significance (VUS) were identified in seven patients who also carried a P/LP variant. VUS alone was detected in 21 patients (21/99 = 21.2%). Among the P/LP pathogenic variants (PV), BRCA 1 PV were seen in 27 patients (65.8%), BRCA 2 variants in 7 patients (17.1%), ATM variants in 3 patients (7.3%) and RAD51, TP53, CHEK2 and HMMR in 1 patient each. Variants were significantly more common in patients with a family history (FH) of malignancy than those without FH (58.5% versus 29.5%; p = 0.013). Age and triple-negative histology were not found to be significantly associated with the occurrence of P/LP PVs. Conclusion: We report a 41% P/LP variant rate in our selected cohort of breast cancer patients, with variants in BRCA constituting 83% and non-BRCA gene variants constituting 17%.

Demographic and clinical profile of 1106 adult soft tissue sarcoma patients: A single institutional prospective database experience from India.

BACKGROUND: Adult soft tissue sarcomas (STS) are rare and diverse. Current management is based on limited literature from the West. Therefore, data from different geographical regions is required, including the low-middle-income countries. This is our experience managing adult sarcomas in the tertiary cancer center of North India. MATERIALS AND METHODS: This is a retrospective analysis of the structured sarcoma database of patients treated in the surgical oncology department between 1992 and 2020. The descriptive analysis includes demography, site distribution, diagnosis, histopathology variations, prior surgical interventions, and stage. RESULTS: A total of 1106 soft tissue sarcoma patients were treated in three decades. Age distribution was 13%, 43%, 31%, and 11% in <20, 21-40, and 41-60 and >60 years, respectively. The male-to-female ratio was 1.73. The anatomical distribution was 17%, 42%, 23%, 7%, 7%, and 3% in upper extremity, lower extremity, trunk, retroperitoneum, head and neck, and viscera, respectively. Overall, 49% of patients had undergone prior suboptimal surgeries at community hospitals. Common histology subtypes were synovial sarcoma (18%), undifferentiated pleomorphic sarcoma (UPS) (13%), dermatofibrosarcoma protuberans (12%), and liposarcoma (9%). A pathological discordance of 13% was identified between the initial and the final histologies. Overall, 61% of tumors were high-grade. Memorial Sloan Kettering Stages II and III were present in 33% and 35% of patients, respectively. CONCLUSIONS: This is one of the largest single institutional experiences of STS from the Asian population. Mostly young adults were affected with male preponderance. The lower extremity and trunk were common subsites. Frequent histologies were synovial sarcoma and UPS. A high rate of suboptimal surgical intervention at the community level and pathological discordance was noted. This study highlights the need to establish prospective structured databases for capturing quality information related to rare malignancies and providing insights for future research.

Clinicopathological Profile and Survival Outcomes in Patients with Localised Extremity Synovial Sarcomas.

AIMS: Synovial sarcoma is a rare but aggressive variant of soft-tissue sarcoma. Literature is sparse and reported mostly from the West. We analysed the clinical profiles and prognostic factors of extremity synovial sarcoma patients in order to study their clinical journey. MATERIALS AND METHODS: This was a retrospective analysis. All patients with extremity synovial sarcoma treated between 1992 and 2020 were included. Patients with metastases at presentation were excluded. A descriptive analysis of demographic and clinicopathological features of patients undergoing limb salvage surgery (LSS) or amputation was carried out. Overall survival and disease-free survival were calculated for the entire cohort as well as for the LSS and amputation groups. Factors prognostic for survival were identified. RESULTS: In total, 157 patients had localised extremity synovial sarcoma. Predominantly, young adults (median 31 years) and males (61%) were affected. Over 70% of patients presented after recurrence or unplanned surgeries. Sixty-seven per cent of tumours were >5 cm, 69% were deep and 23% involved bone. The limb salvage rate was 64%. In the LSS group, adjuvant radiotherapy and chemotherapy were given to 72% and 68% of patients, respectively. In the amputation group, 72% of patients received adjuvant chemotherapy. In a median follow-up of 59 months, 39.4% of patients had recurrences, the majority (61.2%) were systemic. Five-year overall survival and disease-free survival were 53.4% and 49.8%, respectively. Overall survival was 63.9% and 29.7% in the LSS and amputation groups, respectively. On multivariate analysis, tumour size, depth, omission of radiotherapy and bone invasion were found to be the adverse prognostic factors. CONCLUSION: This is one of the largest studies on extremity synovial sarcoma. Mostly males and young adults were affected. The limb salvage rate was 64%, despite most being referred after unplanned surgery. Almost 70% of patients received radiotherapy and chemotherapy. Overall survival was inferior in the amputation group. Tumour size >5 cm, depth and bone invasion were negative, whereas adjuvant radiotherapy was a positive prognostic factor for survival. Chemotherapy had no impact on survival.

Malignant Chest Wall Tumors: Complex Defects and Their Management-A Review of 181 Cases.

BACKGROUND: Chest wall tumors are a heterogeneous group of tumors that are managed by surgeons from diverse specialties. Due to their rarity, there is no consensus on their diagnosis and management. MATERIALS: This retrospective, descriptive analysis includes patients with malignant chest wall tumors undergoing chest wall resection. Tumors were classified as primary, secondary, and metastatic tumors. The analysis includes clinicopathological characteristics, resection-reconstruction profile, and relapse patterns. RESULTS: A total of 181 patients underwent chest wall resection between 1999 and 2020. In primary tumors (69%), the majority were soft tissue tumors (59%). In secondary tumors, the majority were from the breast (45%) and lung (42%). Twenty-five percent of patients received neoadjuvant chemotherapy, and 98% of patients underwent R0 resection. Soft tissue, skeletal + soft tissue, and extended resections were performed in 45%, 70%, and 28% of patients, respectively. The majority of patients (60%) underwent rib resections, and a median of 3.5 ribs were resected. The mean defect size was 24 cm2. Soft tissue reconstruction was performed in 40% of patients, mostly with latissimus dorsi flaps. Rigid reconstruction was performed in 57% of patients, and 18% underwent mesh-bone cement sandwich technique reconstruction. Adjuvant radiotherapy and chemotherapy were given to 29% and 39% of patients, respectively. CONCLUSIONS: This is one of the largest single-institutional experiences on malignant chest wall tumors. The results highlight varied tumor spectra and multimodality approaches for optimal functional and survival outcomes. In limited resource setting, surgery, including reconstructive expertise, is very crucial.

Bilateral Breast Cancer: Clinical Profile and Management.

There is paucity of literature regarding the demography, histopathology, management, and outcomes of bilateral breast cancer (BBC). We present our experience of treating 127 BBC with multimodality management. An audit of prospectively maintained computerized breast cancer database of the department of surgical oncology at a tertiary care center was performed. Demography, clinical profile, molecular sub-types, treatment patterns, and outcomes were analyzed. A total 127 patients presented with BBC between 1992 and 2019. Ninety-four had metachronous (MBBC) and 33 had synchronous breast cancer (SBBC). Most contralateral breast cancer (CBC) patients had early-stage breast cancer in comparison to the index side cancer (37% vs 32%). Ninety-four patients underwent bilateral mastectomy and only 18 patients underwent bilateral breast conservation. Seventy-one patients undergoing BCS and surgery for LABC were given postoperative radiotherapy. All patients received adjuvant chemo- and/or hormonal therapy both for index and CBC based on the stage and hormone receptor status. Thirty-three percent of patients had either locoregional or distant relapse. The 5-year overall survival (OS) and 5-year disease-free survival (DFS) of the entire cohort were 86.6% and 68.4% respectively. There was no difference in the OS and DFS between SBBC and MBBC. The incidence of BBC is expected to increase with effective diagnostic and therapeutic interventions and improving survival. Patients require individualized treatment planning in a multidisciplinary treatment setting.

Neoadjuvant chemotherapy with or without anthracyclines in combination with single HER2-targeted therapy in HER2-positive breast cancer.

BACKGROUND: Neoadjuvant chemotherapy (NACT) with human epidermal growth factor receptor 2 (HER2) blockade is the preferred approach for treating early and locally advanced HER2-positive breast cancer. There is a lack of robust data comparing pathological complete response (pCR) and survival outcomes in anthracycline-free and anthracycline-containing regimens with single HER2-targeted therapy. OBJECTIVES: The present study retrospectively evaluated pCR between two groups: Single HER2-targeted therapy with and without anthracycline. METHODS: A total of 215 HER2-positive female breast cancer patients were analyzed who received eitheranthracycline-containing EC-TH (epirubicin and cyclophosphamide, followed by docetaxel and trastuzumab)oranthracycline-free TCH [docetaxel, carboplatin and trastuzumab]. Univariate and multivariate analyses identified prognostic factors for survival and pCR.Kaplan Meier survival curvesdetermined disease-free survival(DFS) and overall survival (OS). RESULTS: Baseline characteristics were comparable in both treatment groups. The pCR rate was 30.8% in the anthracycline-containing EC-TH group and 40.9% in the anthracycline-free TCH group; p = 0.140. Disease-free survival at 3 years (65.8% vs. 58.4%) and 5 years (49.2% vs. 55.2%) was similar between EC-TH and TCH groups, respectively (log-rank p = 0.550). Three-year (95.5% vs. 92.5%) and five-year (84.4% vs. 80.8%) OSwere also comparable between both groups (log-rank p = 0.485). The anthracycline-containing EC-TH group had a higher incidence of febrile neutropenia (6.4%. vs. 3.6%) and cardiac adverse events (7.7% vs. 4.4%) than the anthracycline-free TCH group. CONCLUSION: Neoadjuvant anthracycline-free chemotherapy has similar pCR and survival outcomeswith favourable cardiac and non-cardiac adverse effect profiles compared with anthracycline-containing chemotherapy.

High-dose-rate remote brachytherapy for metachronous second primary carcinoma of soft palate by iridium 192 isotope in an afterload surface mold.

Conservative management of metachronous second primary carcinoma of head and neck is preferred in order to preserve form and function. The purpose of the case report is to describe the treatment of metachronous second primary carcinoma of soft palate by high-dose-rate, remote, afterload brachytherapy. The brachytherapy was done in remote settings by afterloading Iridium 192 isotope carried through a custom fabricated surface mold. The mold enabled good adaptation, stability, and repeatable positioning of the radiation source at each treatment session of fractionated brachytherapy offering consistent dosimetric advantage through a single dosimetry calculation. Collaborative efforts of radiation oncologist and prosthodontist ensured conservative treatment in outpatient set up with minimal adverse effects.

A Prospective Study Comparing the Role of 18 FDG PET-CT with Contrast-Enhanced Computed Tomography and Tc99m Bone Scan for Staging Locally Advanced Breast Cancer.

Locally advanced breast cancer (LABC) patients require an accurate staging of the disease to rule out distant metastases. Various imaging investigations are used to stage LABC patients. The present study is a prospective comparison of conventional imaging (CI) with fusion positron-emission tomography and computed tomography (PET-CT) scans in the staging of LABC patients. Seventy-three consecutive LABC patients presenting to the breast cancer clinic of the tertiary care cancer institute were included in the study. All patients underwent contrast-enhanced computed tomography, Tv99m bone scintigraphy, and fusion PET-CT. Histology of the metastatic site was confirmed wherever possible. The disparity between the two imaging findings was compared. Doubtful lesions were observed clinically for at least 2 years to confirm their nature. PET-CT detected a higher number of lymph nodes in the axilla, internal mammary, and supraclavicular region as compared to CI. PET-CT upstaged 36.98% and downstaged 5.4% of the patients respectively leading to a change in the management in 30.13% of the patients. Sensitivity, specificity, positive predictive value, and negative predictive value of CI and PET-CT were 71.87%, 87.80%, 82.14%, and 80%, and 90.90%, 90%, 88.23%, and 92.30% respectively. PET-CT was more accurate in staging the LABC patients as compared to CI. PET-CT is more accurate then contrast-enhanced CT and bone scintigraphy for staging locally advanced breast carcinoma patients. It can replace multiple organ-directed imaging in staging breast cancer. It can provide accurate staging of the disease so that patients can be prognosticated and can be directed to the most appropriate treatment plans.

The Impact of COVID-19 on Cancer Care in the Post Pandemic World: Five Major Lessons Learnt from Challenges and Countermeasures of Major Asian Cancer Centres.

OBJECTIVE: The COVID-19 pandemic has dramatically affected healthcare services around Asia. The Asian National Cancer Centres Alliance and the Asia-Pacific Organisation for Cancer Prevention collaborated to assess the mid- and long- term impact of COVID-19 to cancer care in Asia. METHODS: The two entities organised a combined symposium and post-meeting interactions among representatives of major cancer centres from seventeen Asian countries to outlining major challenges and countermeasures. RESULTS: Participating stakeholders distilled five big questions. 1) "Will there be an explosion of late-stage cancers after the pandemic?" To address and recover from perceived delayed prevention, screening, treatment and care challenges, collaboration of key stakeholders in the region and alignment in cancer care management, policy intervention and cancer registry initiatives would be of essential value. 2) "Operations and Finance" The pandemic has resulted in significant material and financial casualties. Flagged acute challenges (shortages of supplies, imposition of lockdown) as well as longer-standing reduction of financial revenue, manpower, international collaboration, and training should also be addressed. 3) "Will telemedicine and technological innovations revolutionize cancer care?" Deploying and implementing telemedicine such as teleconsultation and virtual tumour boards were considered invaluable. These innovations could become a new regular practice, leading to expansion of tele-collaboration through collaboration of institutions in the region. 4) "Will virtual conferences continue after the pandemic?" Virtual conferences during the pandemic have opened new doors for knowledge sharing, especially for representatives of low- and middle-income countries in the region, while saving time and costs of travel. 5) "How do we prepare for the next pandemic or international emergency?" Roadmaps for action to improve access to appropriate patient care and research were identified and scrutinised. CONCLUSION: Through addressing these five big questions, focused collaboration among members and with international organisations such as City Cancer Challenge will allow enhanced preparedness for future international emergencies.
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Retrospective analysis of surgically treated cases of squamous cell carcinoma vulva.

CONTEXT: Vulvar carcinoma accounts for 3%-5% of gynecologic malignancies. The past three decades has observed changes in the trends of clinical characteristics and treatment modalities used in managing this disease. AIMS: The aim of the present study is to analyze the clinic-pathological characteristics and survival of women with squamous cell carcinoma vulva who underwent primary surgical management. SETTINGS AND DESIGN: This was a retrospective observational study. SUBJECTS AND METHODS: Case records of 30 consecutive patients with squamous cell carcinoma of vulva during the period of 2010-2016 were retrospectively reviewed and their clinical profile, treatment details, complications, and survival were analyzed. STATISTICAL ANALYSIS USED: Kaplan-Meier survival analysis, followed by logrank test, was used for survival outcome, and Cox proportional hazard model was used to assess significant risk factors. RESULTS: The mean age of patients was 58 ± 12.9 years. The most common symptom was growth over vulva (73.3%), itching (63.3%), and nonhealing vulval ulcer (26.6%). The most common site for disease was labia majora. The surgical treatments ranged from wide local excision to radical vulvectomy. Postoperative adjuvant therapy was required for 16 patients. The median (95% confidence interval [CI]) overall survival was 27 (21.7-32.2) months. Five-year survival probability for early-stage disease (I + II) was 49% (95% CI: 12.9, 78.4) and for advanced disease (III + IV) was 24.8% (95% CI: 4.8, 42.6). Lymph node-positive status was found to have a significant impact on survival (hazard ratio of 4.9 [95% CI: 1.15-21.02, P = 0.02]). CONCLUSIONS: Despite advances in detection and management modalities, the survival for vulval malignancies has not improved.

Brachytherapy practice during the COVID-19 pandemic: a review on the practice changes.

The COVID-19 pandemic has caused a havoc across the globe, and has significantly affected oncology services, especially radiation therapy due to the need of social distancing as a measure for the pandemic mitigation. Brachytherapy, being an integral part of radiation therapy, posts a dilemma related to the practice of evidence-based oncology. It requires a significant amount of resources and personnel, thereby increasing the risk of exposure to the virus. There has been a significant amount of papers published providing the best available alternatives to external radiation; however, there is a lack of literature on the practice of brachytherapy. In times of the pandemic, deploying brachytherapy as a treatment modality can act as a double-edged sword and therefore, judicious use is warranted in such times of crisis. In this article, we provide a comprehensive review of the role of brachytherapy in various forms and different malignancy sites.

DOSE ASSESSMENT FOR ATMOSPHERIC DISCHARGE OF LONG-LIVED RADIONUCLIDES IN NUCLEAR POWER PLANT DECOMMISSIONING.

Decommissioning of nuclear power plants is a multistage process involving complex operations like radiological characterization, decontamination and dismantling of plant equipment, demolition of structures, and processing and disposal of waste. Radioactive effluents released into the environment may result in exposure of population through various exposure pathways. The present study estimates the public dose due to atmospheric discharge of important radionuclides during proposed decommissioning activities of Indian Pressurized Heavy Water Reactors. This study shows that major dose contributing radionuclides are 60Co followed by 94Nb, 134Cs, 154Eu, 152Eu, 133Ba, 99Tc, 93Mo and 41Ca. It is found that infant dose is higher than adult dose and major fraction of total dose (~98%) is through ground shine and ingestion; other pathways such as inhalation and plume shine contribute only a small fraction. This study will be helpful in carrying out radiological impact assessment for decommissioning operations which is an important regulatory requirement.

Vulvar cancer: surgical management and survival trends in a low resource setting.

BACKGROUND: This study aims to analyze risk factors, clinical profiles, treatment protocols, and disease outcomes in histologically proven resectable vulvar cancer (VC) patients according to tumor stage. This is a retrospective analysis of a prospectively collected database of 20 VC patients from May 2014 to June 2019. RESULTS: The mean age of VC diagnosis was 55 years, with a range of 38-84 years. The incidence was four cases per year. The disease incidence was significantly more in post-menopausal (65%) and multiparous (90%) women. According to FIGO staging of vulvar cancer, stages I, II, and III were assigned to 6, 1, and 11 patients respectively. Two patients suffered from stage IVa vulvar melanoma. All patients had undergone surgical interventions. Patients treated with only nonsurgical (chemotherapy/radiotherapy/chemo-radiotherapy) treatment modalities were excluded from the study. Fifteen patients were treated with wide local excision (WLE), bilateral inguinofemoral dissection (B/L IFLND), and primary repair. Four and one patients were treated with radical vulvectomy (RV) and modified radical vulvectomy (MRV) [with or without B/L IFLND and PLND] respectively. Reconstruction with V-Y gracilis myocutaneous and local rotation advancement V-Y fasciocutaneous flaps were done in two patients. Therapeutic groin nodal dissection was performed in 19 patients except in one patient who was treated by palliative radical vulvectomy. In the final histopathology reports, tumor size varies from 0.5 to 6.5 cm (mean 3.35 cm) with the predominance of squamous cell carcinoma (18 out of 20 patients). Only 10 out of 18 eligible patients received adjuvant treatment. Poor patient compliance has been one of the major reasons for adjuvant treatment attrition rate. Systemic and loco-regional metastasis occurred in 3 patients each arm respectively. Poor follow up of patients is the key limitation of our study. CONCLUSION: Vulvar cancer incidence was significantly high in post-menopausal and multiparous women. The most important prognostic factors were tumor stage and lymph node status. Oncological resection should be equated with functional outcome. The multidisciplinary team approach should be sought for this rare gynecological malignancy.

Effect of intravenous administration of zoledronic acid on jaw bone density in cases having skeletal metastasis: A prospective clinical study.

AIM: The objective is to evaluate the effect of intravenous (i.v.) administration of bisphosphonate (zoledronic acid) therapy on the jaw bone density and incidence of any other bony patholog. SETTINGS AND DESIGN: Observational - prospective study. MATERIALS AND METHODS: A total of 57 patients having a history of bony metastasis (excluding the jaw bone) were enrolled following the inclusion/exclusion criteria. Each patient received six doses of 4 mg i.v. bisphosphonate once a month. Multidetector computed tomography (MDCT) of jawbones for each patient was performed before the start of therapy (baseline) and subsequently at 6 and 12 months. Bone density was assessed at 24 predetermined sites (8 sites in maxilla and 16 sites in mandible) and any pathological change in either of the jaw bones was noted. STATISTICAL ANALYSIS USED: Shapiro-Wilk test ,Pearson's Chisquare test and repeated measures analysis of variance. RESULTS: The result showed no statistically significant increase in mean bone density over a period of 1 year in maxilla and mandible. However, a significant increase in bone density was observed from 6 months to 1 year in mandibular anterior cancellous bone. The detailed observation of each MDCT scan showed no pathological change in either of the jaw bones during the study period. CONCLUSION: The administration (i.v.) of six doses of 4 mg bisphosphonate did not lead to a significant change in bone density over a period of 1 year.

Clinicopathological profile of breast cancer: An institutional experience.

INTRODUCTION: This study was undertaken to evaluate the clinicopathological characteristics of patients with breast cancer at our institute, a tertiary-care cancer center in northern India. MATERIALS AND METHODS: This retrospective study included all patients with breast cancer registered at our institute from January 1st, 2014 to December 31st, 2016. We retrieved data (demographic, baseline clinical characteristics, pathology, and treatment details) from prospectively maintained clinical case records. Patients with incomplete case records or missing baseline information were excluded. RESULTS: We included 550 patients with breast cancer. The median age was 48 years (23-85). The median clinical tumor size was 5.0 cm. The TNM (AJCC-7th edition) stage distribution was stage I, 22 (4%); stage II, 182 (33%); stage III, 247 (44.9%); and stage IV, 99 (18%). Locally advanced breast cancer constituted 40% of the cases. Bone (48 [48.5%]) was the most common site for metastasis followed by lung. Infiltrating ductal carcinoma (528 [96%]) was the most common histologic subtype. Majority of patients, 325 (59%), were positive for estrogen receptor/progesterone receptor whereas 160 (29%) patients were HER2/neu positive. Triple negative breast cancer (TNBC) constituted 28% (154) of patients. In the nonmetastatic subgroup, 343 (76%) patients underwent modified radical mastectomy. Neoadjuvant chemotherapy (NACT) was given in 120 (26.6%) patients, of these 23 (19%) achieved pathological complete remission. Sequential anthracyline and taxane were used as NACT/adjuvant chemotherapy in most cases. Of the eligible patients, 48 (30%) received anti-HER2/neu therapy. CONCLUSION: This is one of the largest comprehensive data from a single center in India. Majority of our patients are younger in age and have advanced disease. TNBC and HER2/neu positive breast cancer are more common in our population.