Survival outcomes with 12 weeks of adjuvant or neoadjuvant trastuzumab in breast cancer

Background: There is limited access to 1 year of adjuvant trastuzumab in resource-constrained settings. Most randomized studies have failed to prove non-inferiority of shorter durations of adjuvant trastuzumab compared to 1 year However, shorter durations are often used when 1 year is not financially viable. We report the outcomes with 12 weeks of trastuzumab administered as part of curative-intent treatment. Methods: This is a retrospective analysis of patients treated at Tata Memorial Centre, Mumbai, a tertiary care cancer center in India. Patients with human epidermal growth factor receptor (HER2)-positive early or locally advanced breast cancer who received 12 weeks of adjuvant or neoadjuvant trastuzumab with paclitaxel and four cycles of an anthracycline-based regimen in either sequence, through a patient assistance program between January 2011 and December 2012, were analyzed for disease-free survival (DFS), overall survival (OS), and toxicity. Results: A total of 102 patients were analyzed with a data cutoff in September 2019. The median follow-up was 72 months (range 6–90 months), the median age was 46 (24–65) years, 51 (50%) were postmenopausal, 37 (36%) were hormone receptor-positive, and 61 (60%) had stage-III disease. There were 37 DFS events and 26 had OS events. The 5-year DFS was 66% (95% Confidence Interval [CI] 56–75%) and the OS was 76% (95% CI 67–85%), respectively. Cardiac dysfunction developed in 11 (10.7%) patients. Conclusion: The use of neoadjuvant or adjuvant 12-week trastuzumab-paclitaxel in sequence with four anthracycline-based regimens resulted in acceptable long-term outcomes in a group of patients, most of whom had advanced-stage nonmetastatic breast cancer.

Access to HER2?targeted therapy at a tertiary care center in India: An evolution

Background:In a previous retrospective audit from our institution we reported that patients had limited access to HER2-targeted therapy due to financial constraints. Subsequently, the advent of biosimilar versions of trastuzumab and philanthropic support has potentially changed this situation. Herein, we reanalyzed and reported access to HER2-targeted therapy in a more recent cohort of patients. Methods: Medical records of new breast cancer patients registered in one calendar year were retrospectively reviewed, supplemented by online pharmacy data to extract information on receptor status, use of HER2-targeted therapy, and other relevant variables. Since not all HER2 immunohistochemistry (IHC) 2+ tumors underwent fluorescent in-situ hybridization (FISH) testing, we estimated the probable HER2 amplified from this group based on a FISH amplified fraction in those HER2 2+ tumors who did undergo FISH. Results: Between January 2016 and December 2016, 4717 new BC patients were registered at our institution, of whom 729 (20.04%) had HER2 IHC 3+ tumors while 641 (17.62%) had HER2 IHC 2+ tumors. The final number of HER2 overexpressing/amplified tumors was estimated to be 928 (729 HER2 IHC 3+, 105 known FISH amplified, and 94 estimated FISH amplified), of whom 831 received treatment at our institution. Overall 474 (57.03%, 95% confidence interval [CI] 53.6–60.4) of these 831 patients received trastuzumab for durations ranging from 12 weeks to 12 months in the (neo)adjuvant setting or other durations in metastatic setting compared to 8.61% (95% CI 6.2–11.6) usage of HER2-targeted therapy in the 2008 cohort. Conclusion: Access to HER2-targeted therapy has substantially increased among patients treated at a public hospital in the past decade, likely due to the advent of biosimilars, the use of shorter duration adjuvant regimens, and philanthropic support. However, further efforts are required to achieve universal access to this potentially life-saving treatment.

Utility of YWHAE fluorescent in-situ hybridisation in mesenchymal tumors of uterus- An initial experience from tertiary oncology centre in India

Background: Endometrial stromal sarcoma (ESS) is a common uterine mesenchymal malignancy. According to World Health Organisation (WHO) 2014 classification, ESSs are further subdivided into low-grade ESS (LGESS) and high-grade ESS (HGESS). HGESS is defined by the presence of YWHAE gene rearrangement and has a poorer prognosis compared to LGESS. METHODS: Twenty-four cases comprising of 16 endometrial stromal sarcoma and 8 lesions mimicking ESS were retrieved from the archives of the Department of Pathology and subjected to fluorescent in situ hybridization (FISH) analysis for YWHAE gene rearrangement. Immunohistochemistry for CD10, ER, PR, Cyclin D1, SMA, H-Caldesmon, Desmin, Ki-67, and Pan Cytokeratin was performed. RESULTS: Two cases with histological features similar to HGESS were positive for YWHAE gene rearrangement while 1 was indeterminate. No cases of LGESS and histological mimics of ESS were positive for this rearrangement. CONCLUSIONS: HGESSs are defined by the presence of YWHAE rearrangement. These tumors present at higher stage and have poorer prognosis. They may not respond to hormonal therapy and may be treated with chemotherapy. Cyclin D1 though not specific remains a sensitive tool to triage endometrial stromal sarcomas for this FISH study.

A comparative analysis of quality of life after postoperative intensity-modulated radiotherapy or three-dimensional conformal radiotherapy for cervical cancer

AIMS: The aim of this study is to compare the quality of life (QOL) between adjuvant three-dimensional conformal radiotherapy (3DCRT) or intensity-modulated radiotherapy (IMRT) for cervical cancer. MATERIALS AND METHODS: QOL assessment was done at the baseline and then longitudinally after completing (chemo) radiation. All patients completed EORTC QLQ-C30 and EORTC QLQ Cx-24 modules. Independent-sample t-test was used to compare the mean scores between the two groups. Analysis of variance was used to compare differences in QOL measures over the six time points (baseline, post-RT, 3, 6, 9, and 12 months after treatment) and between treatment groups (3DCRT vs. IMRT). Linear mixed model was also performed to account for attrition. RESULTS: Overall, 64 patients (image-guided IMRT, n = 40 and 3DCRT, n = 24) completed QOL assessment. The median age and follow-up period were 48 years and 15.5 months, respectively. General QOL domains such as emotional (at 12 months, P = 0.04) and social (at 3 months, P = 0.02 and 12 months, P = 0.03) were better with IMRT. Pain (12 months, P = 0.03); fatigue (12 months, P = 0.05); nausea and vomiting (12 months, P = 0.03); insomnia (post-RT, P = 0.05 and 12 months, P = 0.03); appetite loss (post-RT and 12 months, P = 0.04); and diarrhea (6 months, P = 0.02 and 12 months, P = 0.003) scores were significantly better with IMRT. On linear mixed model analysis, there was a significant interaction between treatment cohort and assessment intervals for physical, emotional, and social functioning, appetite loss, diarrhea, lymphedema, and menopausal symptom scores were significantly better with IMRT. CONCLUSIONS: Treatment technique (IMRT vs. 3DCRT) impacts early QOL in undergoing adjuvant radiation for cervical cancer.

Outcomes of advanced epithelial ovarian cancer treated with neoadjuvant chemotherapy

Background: Ovarian cancer is the fourth most common cancer in Indian women. Majority of these are epithelial ovarian cancers (EOCs), most of which present in advanced stage. Women with poor performance status and/or those unlikely to achieve optimal debulking at upfront surgery, benefit from neoadjuvant chemotherapy (NACT) followed by interval cytoreduction, with lesser surgical morbidity and equal survival rates as compared to primary cytoreduction. Methodology: This was a retrospective analysis of patients with advanced ovarian cancer, treated with NACT followed by interval debulking surgery at Tata Memorial Hospital from January 2014 to December 2014. Results: Epithelial cancers constituted 84.4% (n = 406) of all cases of ovarian malignancies. Of these, overwhelming majority (84.3%, n = 342) were in the advanced stage. Sixty percent of all EOC patients received NACT. The mean baseline serum CA-125 level in women treated with NACT was 4294.7 U/ml (range, 11–151,200 U/ml). The median number of NACT cycles (paclitaxel + carboplatin) was 3. Optimal cytoreduction was achieved in 81.5% cases. The rates of Grade 3 or 4 intraoperative and postoperative complications were 4% each. The median postoperative stay was 5 days and the median time between surgery and adjuvant chemotherapy was 20 days. The median progression-free survival (PFS) was 15.15 months (95% confidence interval [CI]: 12.95–17.34), and the median overall survival (OS) was 34.73 months. Multivariate analysis revealed that optimal cytoreduction (hazard ratio [HR] = 2.04 [95% CI: 1.15–3.62]; P = 0.015) and number of NACT cycles (3 vs. >3; HR = 1.51 [95% CI: 1.06–2.16]; P = 0.022) were significantly associated with PFS, and optimal cytoreduction (HR = 3.21 [95% CI: 1.53–6.73]; P = 0.002) and ECOG status (0–1 vs. ≥2; HR = 2.64 [95% CI: 1.25–5.55]; P = 0.011) with OS. Conclusions: High rates of optimal cytoreduction were achieved at interval cytoreductive surgery after NACT, with acceptable surgical morbidity, early start of adjuvant chemotherapy, and survival outcomes comparable to international standards.

Locally advanced cervical cancer: A study of 5-year outcomes

Background: Cervical cancer is the second most common cancer among Indian women. This present retrospective study was conducted to report patient outcomes with locally advanced cervical cancer treated in the year 2010. Materials and Methods: Case records of cervical cancer patients registered from January 1, 2010, to December 31, 2010 were retrieved. A total of 1200 patients were registered, of which 583 received either definitive or adjuvant radiotherapy (RT). Of these, 345 patients who received complete treatment at our hospital were included for outcome analysis. Descriptive statistics were used to summarize patient- and treatment-related variables, and Kaplan–Meier analysis was performed for survival analysis. Results: The median age was 56 years (range: 33–90). Squamous carcinoma was the most common histology (91.4%) and the majority were FIGO Stage III (45.4%). Median follow-up of the cohort was 44 months (1–85 months). The 5-year disease-free survival (DFS) across stages was 50%. Most important predictor of DFS was FIGO staging (Stage II vs. Stage III: 62% vs. 45%) and use of concurrent chemoradiotherapy (CTRT) l (RT vs. CTRT: 32% vs. 57%, respectively). Patients aged >70 years had a significantly poor DFS at 5 years; however, did not have any effect on survival. Grade 3 or more late toxicity was seen in only 5% of the patients. Conclusion: Five-year DFS of 62% and 45% of Stage II and III patients treated under routine care represents comparable stage-matched results to the rest of the world, respectively.

Analysis of bone and soft-tissue sarcomas registered during the year 2012 at Tata Memorial Hospital, Mumbai, with clinical outcomes

ntroduction: Primary bone and soft tissue sarcomas are rare, but diagnostically and therapeutically challenging group of tumors, requiring multidisciplinary management. There are limited documented studies from multidisciplinary teams , in the form of comprehensive analysis of these tumors, from our country. This study is an analysis of cases of osteosarcomas, Ewing sarcomas (ESs), chondrosarcomas (CSs), and soft-tissue sarcomas (STSs), registered at our institution during 2012. Methods: Clinical details, including outcomes of cases of bone and STSs, during the year 2012, were retrieved from the medical records of our institution and were further analyzed. Results: Ninety-five high-grade, extremity-based, treatment-naïve cases of osteosarcomas were treated with a novel, dose-dense, nonhigh-dose methotrexate-based OGS-12 protocol. Good histopathologic response (necrosis ≥90%) was achieved in 59% nonmetastatic and 56% metastatic patients. At a median follow-up of 48 months, the estimated 5-year event-free survival and overall survival (OS) were 67% and 78%, respectively. In the metastatic cohort at a median follow-up of 51 months, the 5-year estimated progression-free survival was 24% and OS was 26%. Among 87 (73.2%) nonmetastatic and 32 (26.8%) metastatic, analyzable cases of ES, at a median follow-up of 40 months, the disease-free survival (DFS) and OS in the nonmetastatic group were 62% and 83%; in the metastatic group, they were 37.5% and 65.6%, respectively. Among 40 cases of CSs (33 nonmetastatic and 7 metastatic), 21 had limb salvage surgery while 5 had amputation. Microscopically, 90.4% were Grade II CSs. Five-year OS and DFS were 84.6% and 71%, respectively. Among 189 high-grade, extremity-based STSs (89% nonmetastatic), synovial sarcoma was the most common subtype (31%). Eighty-five percent had limb preservation surgery; a majority were offered adjuvant radiation with or without chemotherapy. At a median follow-up of 51 (1–63) months, 3-year local control, DFS, and OS were 81%, 48%, and 64%, respectively. Conclusions: The novel OGS 12 and Ewing Family of Tumors 2001 protocols have shown comparable outcomes to international standards in cases of osteosarcoma and ES, respectively, and merit wider applications, especially in low- and middle-income countries (LMICs). Outcomes in STS and CSs were also comparable and underscore the importance of a multidisciplinary approach for the management of sarcomas in LMICS.

Surgical morbidities and outcomes of major salivary gland neoplasms treated at a tertiary cancer center

Background and Objectives: Salivary gland neoplasms are relatively uncommon. They have a wide variety of histopathological types with diverse biological behavior. It involves all the major and minor salivary glands in the head and neck. This article focuses on the various types of major salivary gland tumors treated at a tertiary cancer center along with their surgical morbidities and outcomes. Materials and Methods: Data of all the salivary gland neoplasms operated in the head and neck services between January 2012 and December 2013 were retrieved from a prospectively collected database. The clinical, demographic data and types of surgeries along with the morbidities were collated from the database and the details regarding the follow-up were collected from the electronic medical record. Results: Out of 235. cases registered, 107. patients were treated at our institute. The parotid gland was most commonly involved; majority were malignant lesions. Sixty-two patients were treatment naive at presentation. Majority presented with advanced disease. Superficial parotidectomy was the most common surgery performed and neck dissection was done in 27. patients. Facial nerve palsy was the most common complication following surgery. (16%). Sixty patients received adjuvant treatment. All patients on follow-up were alive at their last visit, with 10. patients having recurrence. Factors influencing the disease-free survival were extracapsular spread, tumor grade, and perineural invasion. Conclusion: The postoperative morbidities and outcomes for major salivary gland neoplasms in our series were acceptable and comparable to the results available in the literature. Appropriate treatment of the salivary gland neoplasm will yield good outcomes with acceptable morbidity.

Role of 18F-fluorodeoxy glucose PET-CT in asymptomatic epithelial ovarian cancer with rising serum CA-125: A pilot study.

Background. We evaluated the role of 18F-fluorodeoxy glucose (FDG) PET-CT scan in the diagnosis of early relapse in patients with epithelial ovarian cancer (EOC) who were asymptomatic but had a rising serum CA-125 level. Methods. Between May 2006 and July 2008, 16 patients with advanced EOC (stages III and IV) who had achieved complete response after cytoreductive surgery and platinumbased chemotherapy were included. These patients were asymptomatic but had a rising serum CA-125 level with normal physical examination and contrast-enhanced CT scan of the abdomen and pelvis. Patients were evaluated with 18F-FDG PET-CT scan. Written informed consent was taken. Patients with a positive PET-CT scan were advised ultrasoundguided fine-needle aspiration cytology (FNAC) from the area showing increased uptake. Patients in whom FNAC was negative or inconclusive or those with negative PET-CT scan were followed up closely for the next 6 months with repeat clinical evaluation and CT scan. Results. Fifteen patients (15/16) had a positive PET-CT scan. In 9 patients the positive PET lesion was confirmed on FNAC, while in 5 patients this was confirmed on follow-up CT scan after 6 months. One patient who had a single positive lesion in the pelvis on PET-CT was initially considered falsepositive because a follow-up CT scan at 6 months did not show the lesion. However, on regular follow-up after 2 years, she was detected to have an isolated lesion in the PET-positive area which was confirmed on secondary cytoreduction. This patient was considered as true-positive in the current analysis. One patient, who had a negative PET-CT scan and a negative CT scan at 6 months’ follow-up was considered true-negative. The sensitivity and specificity of PET-CT scan was 100%. We could confirm positivity on histopathology/FNAC in 10 of the 15 (66.7%) true-positive cases. Conclusion. 18F-FDG PET-CT scan is a sensitive and specific technique for early diagnosis of relapse in asymptomatic EOC patients with rising CA-125. However, its role in the management of recurrent ovarian cancers needs further evaluation.

Clinico-pathological spectrum of primary ovarian malignant mixed mullerian tumors (OMMMT) from a tertiary cancer institute: A series of 27 cases.

Aims and Objectives: To study the clinico-pathological characteristics of primary ovarian malignant mixed mullerian tumor (OMMMT) and assess the prognostic factors associated with treatment outcome and survival. Materials and methods: The pathology database was searched for primary ovarian carcinosarcoma diagnosed and/or managed at our institute from period of January 2004 to July 2010. The histological sections were reviewed, with emphasis on type and grade of epithelial and sarcomatous components. The medical records were retrospectively analyzed for clinical details and follow up. Results: A total of 27 cases of primary ovarian carcinosarcoma were identifi ed. The median age at diagnosis was 51 years. Fourteen patients had advanced stage (stage III and IV) at presentation. Cytoreductive surgery was done in 18 cases, and 7 had received upfront chemotherapy. Histologically, 10 cases had epithelial predominance (> 50% epithelial component) and 11 had sarcoma predominance. The most frequent epithelial component was endometroid type, and most common sarcoma component was rhabdomyosarcomatous. Hyaline droplets within sarcomatous stroma were seen prominently in 15 cases. Three cases showed germ cell / yolk sac-like areas. Eighteen cases had follow up with a median of 15 months (4-40 months). The recurrence-free survival in advanced stage and sarcoma predominant was 10.5 months in comparison to 13 months in early stage and epithelial predominant OMMMT. Conclusion: Primary ovarian carcinosarcoma is a rare biphasic malignancy with variable proportions of epithelial and spindle elements. Presence of hyaline droplets within spindle sarcoma in a biopsy from ovarian mass should alert the pathologists regarding MMMT. Advanced stage, suboptimal cytoreduction, and sarcoma predominant tumors are likely to have a worse outcome in ovarian MMMT.

Clinicopathological spectrum of 19 adenosarcomas of female genital tract, including uncommon clinical associations and immunohistochemical profile, reviewed at a single institution.

Background: Adenosarcomas of the female genital tract have been rarely documented as case series from our continent. Materials and Methods: Over a seven-year period, 19 adenosarcomas were critically reviewed. Results: Nineteen tumors occurred in the age range of 21-65 years (mean: 43), in the endometrium (8), endometrium and cervix (4), cervix (4), and ovary (3). Four cases displayed coexisting leiomyomas; two, adenomyosis; two on background endometriosis; and one in post-treated cervix carcinoma. Histopathologically, the tumors were low grade (10; 52.6%) and high grade (9; 47.3%), the latter with sarcomatous overgrowth (SO) (7/9 cases). Dedifferentiation (8, 42.1%) and conspicuous decidualization (2) were noted. Immunohistochemically, the tumors focally expressed CD10 (4/6), smooth muscle actin (SMA) (3/8), desmin (8/11); diffuse vimentin (7/7), and estrogen receptor/progesterone receptor (ER/PR) (2/4). Ki-67 (6 cases) varied 5-20%. Seventeen patients underwent surgery and four received adjuvant treatment (3/4 high-grade tumors). Five tumors recurred (4 high-grade tumors with SO) and one metastasized. Among 11 patients, five were alive with disease (AWD) (mean: 29.4 months) and six, free of disease (FOD) (mean: 15 months), the latter mostly with low-grade type tumors (83.3% cases). Conclusions: Diverse clinicopathological spectrum was noted within adenosarcomas. Low-grade tumors were less aggressive than high-grade ones, with SO. Immunohistochemically, lower CD10 and ER/PR positivity was noted in high-grade tumors. Surgery formed the mainstay of treatment. Adjuvant treatment was offered in high-grade subtypes, including in tumors with SO.