Secondary cytoreduction in platinum sensitive relapsed ovarian cancer: an individual patient level meta-analysis.

OBJECTIVE: To synthesize the role of secondary cytoreduction in recurrent ovarian cancer from the results of randomized studies. METHODS: We conducted a meta-analysis of randomized controlled trials which compared secondary cytoreductive surgery versus no surgery in patients with platinum sensitive relapsed ovarian cancer. Individual patient data for overall survival and progression free survival were manually extracted from published survival curves, for whole study populations and subgroups based on completeness of surgical resection and bevacizumab use, using WebPlotDigitizer software. Overall survival and progression free survival curves for each study and the combined population were reconstructed from extracted data. RESULTS: Three studies with 1249 patients were included, of whom complete resection was achieved in 427 (34.2%) patients. In individual patient data analysis of the whole study population with 562 deaths, there was no significant difference in overall survival between the surgery and no surgery groups (median 52.8 vs 52.1 months, respectively, hazard ratio (HR) 0.94, 95% confidence interval (CI) 0.80 to 1.11; p=0.5) but the surgery group had significantly longer progression free survival compared with the no surgery group (median 18.3 vs 14.4 months, respectively, HR 0.70, 95% CI 0.62 to 0.80; p<0.001). In subgroup analyses, overall survival was significantly longer in the complete cytoreduction subgroup compared with the no surgery group (median 62.0 vs 52.1 months, respectively, HR 0.70, 95% CI 0.57 to 0.92; p<0.001) while overall survival was significantly worse in the incomplete cytoreduction subgroup compared with the no surgery group (median 34.2 vs 52.1 months, respectively, HR 1.72, 95% CI 1.38 to 2.14; p<0.001). In the no bevacizumab subgroup, there was no significant overall survival difference between the surgery and no surgery groups (median 49.3 vs 47.0 months, HR 0.86, 95% CI 0.67 to 1.10; p=0.25). CONCLUSIONS: Secondary cytoreductive surgery among women with platinum-sensitive relapsed ovarian cancer did not lead to significant benefit in overall survival although it increased progression free survival. However, overall survival was significantly longer among patients in whom complete cytoreduction was possible compared with no surgery.

Evaluation of outcomes in patients of cervical Cancer with lower one third vaginal involvement: A single institutional experience.

OBJECTIVE(S): The objective of this study was to evaluate the clinical outcomes and prognostic factors affecting survival of cervical cancer patients presenting with lower third vaginal involvement. MATERIALS/METHODS: The patients with histologically proven invasive cervical cancer with clinical FIGO-2009 stage IIIA and IIIB with lower one-third vaginal involvement, treated with radio (chemo) therapy between 2010 and 2016 at our institution were retrospectively analyzed. RESULTS: There were 118 cervical cancer patients with lower third vaginal involvement with median age of 56.5 years (Range: 33-77 years). Forty-five patients were of FIGO stage IIIA, 73 patients staged as stage IIIB at diagnosis with predominant squamous histology. At a median follow up of 30 months, 12 patients (10.1%) developed local vaginal recurrences and 4 patients (3.3%) had developed loco regional recurrences, 27 patients (23%) developed distant and 2 patients developed loco-regional and distant relapses. The 3- year DFS and OS rates were 61.5% and 69.8% respectively. The 3-year DFS and OS of patients with IIIA was significantly better than IIIB patients (71% vs 56%, p: 0.02 and 76% vs 66%, p: 0.01 respectively) on univariate analysis. Concurrent chemotherapy and absence of persistent disease emerged as independent predictors of survival on multi-variate analysis. CONCLUSION: The outcome of patients with FIGO IIIA is better than IIIB with lower vaginal involvement. Elderly patients, patients not receiving concomitant chemotherapy and presence of residual disease at BT are associated with poorer outcomes.

Clinicopathological features of 50 mismatch repair (MMR)-deficient endometrial carcinomas, tested by immunohistochemistry: A single institutional feasibility study, India.

There are few comprehensive studies from Asia on clinicopathologic features of mismatch repair (MMR)-deficient endometrial carcinomas, including rarely from our country. One hundred and four cases of endometrial carcinomas were tested for four MMR proteins by immunohistochemistry. Among 50 MMR-deficient (MMRd) tumors(48%), age-range was 27-68 years(median = 53) and tumor size(n = 34) varied from 1.2-10 cm(average = 4.6). Lower uterine segment(LUS) was involved in 21/31 cases(67.7%). Histopathologically, all cases were endometrioid adenocarcinomas(EMACs), of FIGO grade 2(low-grade)(18 cases) and 3(high-grade)(32 cases), displaying de-differentiated, undifferentiated and lymphoepithelioma(LE)-like patterns, in 24 cases(48%). Tumor infiltration ≥ half of myometrium was seen in 30/44 cases (68.1%); lymphovascular emboli in 19/43 cases(44.1%); and lymph node metastasis in 7/22(31.8%) cases. Uncommonly, clear cell component(n = 2) and focal neuroendocrine differentiation (n = 2) were observed. Immunohistochemically, tumor cells showed paired loss of MLH1 and PMS2 in 33(66%) and MSH2 and MSH6 in 14(28%) cases, along with loss of MSH2 and PMS2, in two and a single case, respectively. Nine patients(18%) were treated for another cancer and 9/33(27.2%) disclosed familial history of cancer. MSH2 was the most frequently lost MMR protein in those cases. Additionally, tumor cells displayed ER positivity in 41/50 cases(82%), PR in 38/41cases(92.6%) and wild-type p53 staining in 24/28 cases(85.7%). Tumor with LE-pattern showed PDLI immunoexpression. Certain clinicopathologic features suggestive for MMRd associated ECs, such as relatively large-sized tumors, involving LUS; especially high-grade, infiltrative EMACs, with undifferentiated/de-differentiated, and LE-like patterns; showing deep muscle invasion, frequent PR immunoexpression and invariably, wild-type p53 immunostaining can be useful in screening cases of Lynch syndrome. This constitutes the first report on these tumors from our country.

Osteosarcoma journey over two decades in India: Small steps, big changes.

BACKGROUND: The management of osteosarcoma is challenging especially in lower-income and middle-income countries, and there is an unmet need to evolve efficient and sustainable chemotherapy regimens. METHODS: We compared the outcomes in nonmetastatic osteosarcoma patients treated with three sequential non-high-dose methotrexate-based combination chemotherapy protocols at a single tertiary care center over two decades. The first protocol, OGS-99, involved dose-intense, alternating dyads of three drugs: doxorubicin (Dox), cisplatin (CDDP), and ifosfamide (Ifo). The second protocol, OGS-99 enhanced, included OGS-99 drugs with etoposide and enhanced supportive care. The OGS-12 protocol involved dose-dense administration of eight sequential dyads of Dox, CDDP and Ifo, universal growth factor prophylaxis and targeted nutritional support. Event-free survival (EFS), overall survival (OS), and toxicity were reported using a retrospective chart review in the OGS-99 and OGS-99 enhanced protocols and prospectively in the OGS-12 protocol. RESULTS: A total of 41, 94, and 385 treatment-naïve, consecutive, nonmetastatic patients with extremity osteosarcoma were treated with the OGS-99 (2000-2005), OGS-99 enhanced (2010), and OGS-12 (2011-2016), respectively. At a median follow-up of 19, 86, and 39 months, the five-year EFS rates were 38%, 50%, and 62% in the OGS-99, OGS-99 enhanced, and OGS-12, respectively. The corresponding rates of five-year OS were nonevaluable, 60% and 77%, respectively, with acceptable rates of grade 3-4 toxicities: febrile neutropenia (40%), thrombocytopenia (36%), anemia (51%), and 1% deaths related to toxicity. CONCLUSIONS: Sequential selection of an intelligent, dose-dense chemotherapy regimen together with enhanced supportive care resulted in marked improvement in outcomes of nonmetastatic osteosarcoma and this "small steps-big changes" model deserves wider recognition and usage.

Five rare cases of Ewing sarcoma, including with epithelial differentiation, involving the female genital tract, displaying EWSR1 rearrangement: Diagnostic challenge and treatment implications.

We present clinicopathological and molecular cytogenetic features of five rare cases of Ewing sarcomas, occurring in the female genital tract. A 40 year-old lady presented with a 5.4 cm-sized vaginal mass of 3 months duration, which was histopathologically diagnosed as ES. She defaulted chemotherapy and 8 months later, presented with a recurrence. She underwent chemotherapy and radiotherapy. A 45 year-old lady presented with recurrent vaginal bleeding, for which she underwent total abdominal hysterectomy (TAH) and unilateral salpingo-oophorectomy (USO), 2 and 1/2 years back. Subsequent vaginal biopsy was reported inconclusively, elsewhere. Thereafter, a 5 cm-sized, residual cervicovaginal mass was reported as ES. She completed induction chemotherapy with a significant response. A 35 year-old-lady was referred with a 4 cm-sized cervical mass, for which she underwent TAH-USO with pelvic and para-aortic lymphadenectomy. A 39 year-old-lady presented with a right labial lesion, which recurred. She underwent initial excision, chemotherapy, wide excision and brachytherapy. A year later, she developed multiple metastases; received palliative radiotherapy and died-of-disease. A 16 year-old girl presented with perineal swelling of 4 months duration. She underwent surgical excision of a recurrent right-sided labial cyst, followed by chemotherapy. On histopathological review, all 5 cases were malignant round cell tumors. Immunohistochemically, tumor cells displayed MIC2/CD99 and Fli1 positivity, along with focal positivity for pan cytokeratin (AE1/AE3) (cases 1 and 2) and p63 (case 2). Furthermore, tumor cells in the 1st, 2nd, 3rd and 5th cases displayed EWSR1 rearrangement. Five uncommon cases of ES involving the female genital tract are presented with diagnostic challenges and therapeutic implications.

Clinical outcomes of adaptive intracavitary and interstitial brachytherapy technique in locally advanced cervical cancer: A real-world data.

PURPOSE: To evaluate clinical outcomes of CT-based adaptive intracavitary and interstitial brachytherapy (IC followed by IC-ISBT) in locally advanced cervical cancer (LACC) in resource-constrained settings. METHODS AND MATERIALS: LACC patients treated with adaptive brachytherapy techniques were analyzed to evaluate treatment characteristics and clinical outcomes. The Kaplan-Meier method was used for survival analysis, and the log-rank test for univariate analysis. RESULTS: Out of 141 eligible patients with LACC, 87 (61.7%) patients received external beam radiotherapy (EBRT) in referral hospitals, while 54 (38.3%) were treated at our center. We divided our cohort into two groups: poor EBRT responder group (n = 70 [49.6%]) where IC-ISBT was adapted to achieve optimum tumor doses and OAR optimization group 71 (50.4%) where IC-ISBT was performed to reduce OAR doses. Median HRCTV-D90 dose was 88 Gy (range 70-109 Gy) with median HRCTV volume 33cc (range 15-96). Median D2cc doses to OARs were 90 Gy (range 70-107), 71 Gy (range 55-105) and 70 Gy (range 47-90) to bladder, rectum and sigmoid, respectively. At median follow-up of 32 months, 3-year local control (LC), locoregional control (LRC), disease-free survival (DFS) and overall survival (OS) were 83%, 75%, 64% and 72%, respectively. Subgroup analysis revealed significantly better outcomes for OAR optimization compared to poor EBRT responders, with 3-year LC (95% vs. 70.1%, p < 0.001), LRC (87.3% vs. 62.7%, p < 0.001), DFS (79.2% vs. 49.4%, p < 0.001), and OS (86.2% vs. 57.4%, p < 0.001) CONCLUSION: In resource-constrained settings, implementation of Adaptive IC-ISBT is a viable alternative for optimizing OAR doses in LACC. However proactive approach employing IC-ISBT for tumor dose-escalation from first fraction of BT is warranted for improving LC in poor EBRT responders.

Clinical outcome of early-stage endometroid adenocarcinoma: a tertiary cancer center experience.

OBJECTIVE: Endometrial cancer (EC) outcome data from developing countries are sparse. We undertook this retrospective analysis to report outcome in our patient population. MATERIALS AND METHODS: Two hundred forty-nine patients with stage I and II and type I histology ECs referred/treated at our institution from 1998 to 2004 were analyzed. All the details including demographic profile, surgical and histopathological details, as well as International Federation of Gynecology and Obstetrics stage and adjuvant therapy were compiled. The 1988 International Federation of Gynecology and Obstetrics staging and risk stratification were performed on the basis of PORTEC risk groups. RESULTS: With a median age of 54 years (26-72 years), 136 patients (55%) underwent surgery elsewhere; 118 (47.3%) underwent a complete surgical staging. There were 60 (24.1%), 124 (49.8%), 65 (26.1%) patients in the low-risk (LR), intermediate-risk (IR), and high-risk (HR) groups, respectively. Adjuvant radiation was given in 160 patients (LR, 18; IR, 85; and HR, 57). With a median follow-up of 36 months (mean, 40 months), 10 patients had vault recurrences, (LR, 3; IR, 4; and HR, 3), 11 had nodal (5 also had local recurrence; LR, 2; IR, 4; and HR, 5), and 16 had distant recurrences (3 also had nodal; LR, 4; IR, 5; HR, 7). The 5-year disease-free survival (DFS) and overall survival (OAS) rates were 80% and 95%, respectively. The DFS and OAS rates at 5 years were 84% and 97%, 85% and 98%, and 60% and 85% for the LR, IR, and HR groups, respectively. On multivariate analysis, grade (P = 0.002) and type of radiation (P = 0.027) had significant impact on DFS and OAS. Late toxicities (grade 3/4) were vaginal stenosis in 4 (1%) and radiation proctitis in 3 (1%) patients. CONCLUSIONS: In our study, ECs are seen in relatively younger population. There is a trend toward incomplete staging surgery outside the oncological referral network. However, the clinical outcome for early-stage type I histology ECs within our population are similar to those reported in the literature.

Role of FDG 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 platinum-based 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 (18)F-FDG PET-CT scan. Written informed consent was taken. Patients with a positive PET-CT scan were advised ultrasound-guided 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 false-positive 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.

CONcurrent ChEmotherapy and RadioTherapy in adjuvant treatment of breast cancer (CONCERT): a phase 2 study.

Purpose: This phase 2 study evaluated the safety of adjuvant chemoradiation (CTRT) for breast cancer. Methods: From April 2019 to 2020, 60 patients with stage II-III invasive breast cancer planned for adjuvant taxane-based chemotherapy and radiotherapy (RT) were accrued. Local ± regional (excluding the internal mammary nodal region) RT (40 Gy in 15 fractions ± boost) was started with the third cycle of an adjuvant taxane in a 3-weekly schedule or with the eighth cycle in a weekly schedule. Results: Thirty-six patients received 3-weekly paclitaxel regimen and 24 received weekly paclitaxel regimen. The commonly used technique was three-dimensional conformal RT which was employed in 58% of patients. Regional RT, including the medial supraclavicular region, was done in 42 patients (70%). No dose-limiting (grade 3 or 4) toxicity was documented and all patients completed CTRT without any treatment interruption. The median ejection fraction pre and post CTRT 6 months was 60% (p = 0.177). The median value of cardiac enzyme (Troponin T ng/L) decreased from 37 to 20 (p = 0.009) post CTRT 6 months. Of the 54 patients who underwent the pulmonary function tests, there was no significant difference in various parameters like functional vital capacity (FVC) (2.29 versus 2.2 L, p = 0.375), forced expiratory volume at 1 second (FEV1) (1.86; 1.82; p = 0.365), FEV1/FVC (81.5; 81.43; p = 0.9) and diffusion lung capacity for carbon monoxide (88.3; 87.6; p = 0.62). At a median follow-up of 34 months, the 3-year actuarial rate of disease-free survival and overall survival was 75% and 98.3%, respectively. Quality of life scores (QOL) improved after treatment for most of the domains comparable to the pre-RT scores. Conclusion: Taxane-based adjuvant CTRT is a safe option and results in minimal toxicity and excellent compliance. It has favourable impact on cardio-pulmonary profile and QOL scores.

Clinical Observations and Outcomes in Advanced Low-Grade Serous Carcinoma of the Ovary: Case Series from a Tertiary Cancer Center.

Low-grade serous carcinoma (LGSC) is a rare histologic subtype of ovarian cancer. We present detailed management of 15 cases of advanced LGSC from a tertiary cancer center of India. Fifteen cases of advanced LGSC who underwent cytoreductive surgery (CRS) were analyzed from a prospectively maintained database. Baseline demographic characteristics, surgical details, and chemotherapy details were recorded. Descriptive statistics were summarized, and progression-free survival (PFS) and overall survival (OS) were estimated. The median age was 37 years. Nine patients had received NACT. All cases were FIGO stage III. Mean PCI was 15. Eleven patients had a completeness of cytoreduction score of 0-1. The median surgical time was 7.5 h; nine patients required multiple gastrointestinal resections. Median blood loss was 2500 ml. Median postoperative ventilation, ICU stay, and hospital stays were 1, 2, and 16 days, respectively. One patient had a grade III complication. Four patients received adjuvant chemotherapy. There was no postoperative mortality at the end of 90 days of surgery. All the patients except one were offered hormonal maintenance therapy. At a median follow-up of 43 months, 4 patients were disease-free, 9 had a recurrence, one died of disease progression, and one was lost to follow-up. Most recurrences were locoregional in the peritoneal cavity or pelvis. Four-year OS and PFS were 71.8% and 29.7%, respectively. Advanced LGSCs occur mostly in young premenopausal women with favorable oncologic outcomes. Optimal CRS is the mainstay of treatment. Relative chemo-resistance and hormone receptor positivity provide an excellent therapeutic opportunity for endocrine therapy.

Early outcomes of abbreviated multi-fractionated brachytherapy schedule for cervix cancer during COVID-19 pandemic.

PURPOSE: Brachytherapy (BT) for cervix cancer was listed as a level I priority and reduced number of implants and multiple fractions were recommended during COVID-19 pandemic. We present early clinical outcome of this approach. METHODS AND MATERIALS: Patients treated with (chemo)radiotherapy and BT with single implant and multiple fractions BT were included. Treatment protocol included 3-5 fractions of 5-8.5 Gy with an aim to achieve point A dose of 70 Gy EQD210Gy (or HRCTV dose of >80 Gy EQD210Gy) in those undergoing intracavitary (IC) and HRCTV dose >85 Gy EQD2 10Gy in patients undergoing Intracavitary-Interstitial (IC/IS) whereas maintaining bladder (B2cc), rectum (R2cc), sigmoid (S 2cc) doses of 90, 75, and 75 Gy EQD23Gy. Time to event analysis was used to report oncological endpoints. Toxicity was reported using crude proportions. RESULTS: From April 2020 to March, 2021, 64 patients with stage IB2-IV received single implant and multi-fraction BT after external radiation of 45 Gy/25 fractions/5 weeks. Only 76.7% (n = 49) received concurrent chemotherapy. Median overall treatment time (OTT) was 56 days (38-131 days). Overall, 62.5% (n = 40) patients received IC and 37.5% (n = 24) received IC+IS. The median HRCTV was 34.7 cc (IQR 25-41). Median (IQR) point A dose, HRCTV D90, B2cc, R2cc, and S2cc for those undergoing IC was 74 Gy (71-78), 80 Gy (73-84), 86 Gy (82-89), 70 Gy (65-74), 65 Gy (59-73) respectively. For the IC+IS cohort, HRCTV D90, B2cc, R2cc, and S2cc was 84 Gy (78-89 Gy), 89 Gy (86-92), 70 Gy (67-74), 68 Gy (59-76). At a median follow-up of 16 months (5-27) the 2-year local control, pelvic control, cause specific and overall survival was 88%, 85.3%, 92.2%, and 81.3% respectively. Late gastrointestinal and genitourinary grade ≥III toxicities were 14% and 1.5% each. CONCLUSIONS: Abbreviated BT outcomes are encouraging for oncological outcomes despite delays in overall treatment time and omission of chemotherapy. Further mature follow up is needed.

Reirradiation with advanced brachytherapy techniques in recurrent GYN cancers.

PURPOSE: To evaluate clinical outcomes of recurrent gynaecological cancers treated with reirradiation (reRT) using advanced brachytherapy (BT) technique. METHODS AND MATERIALS: Seventy-six women who underwent reRT with BT for gynaecological cancers at our institute between January 2000 and December 2019 were analysed to determine patient, disease and treatment characteristics and clinical outcomes. Descriptive analysis was used for demographics, and the Kaplan Meir method was used for survival analysis. RESULTS: Median age at recurrence was 55 years (Range: 35-73). Forty-three patients had recurrent cervical cancer with intact uterus, and 33 had recurrent vault/vaginal cancers post adjuvant RT. Eight patients received EBRT prior to BT (Range: 30-50Gy). Twenty-two patients (28.9%) received salvage chemotherapy before consideration of brachytherapy. Brachytherapy application was done using MUPIT in 38, Vienna applicator in 20, Syed Neblett in 8, central vaginal cylinder in 3, multicatheter intravaginal applicator in 2, tandem-ovoids in 4 and Houdek applicator in 1 patient. Median cumulative EQD2 for all courses of radiation was 108 Gy (IQR 92-123 Gy). At median follow up of 39 months, local control (LC), progression-free survival (PFS) and Overall survival (OS) at 2-years was 60%, 56.3%, and 72.9 respectively. Patients who had recurrences beyond 2 years had significantly better OS compared to early recurrences. Patients who received BT doses >40 Gy had a higher LC and PFS. Grade 3 to 4 late rectal toxicity was seen in 10 (13%), bladder toxicity in 6 (8%) and vaginal fibrosis in 24 (31%) patients. CONCLUSION: The use of advanced BT approach in reirradiation setting is a feasible and safe option in treatment of post-treatment recurrent cervical, endometrial, and vaginal cancers.

Knowledge, Attitudes and Practices Towards COVID-19: A Cross-Sectional Survey.

Aim: To assess the knowledge, attitudes and practices (KAP) regarding the corona virus disease 2019 (COVID-19) pandemic among patients and their attendants visiting the gynaecologic oncology outpatient department (OPD) and to assess the factors associated with a KAP score. Methodology: A KAP cross-sectional survey was conducted over three months exploring KAP relevant to COVID-19. Mann-Whitney U test and Kruskal-Wallis test were used to compare the differences in knowledge, attitude and practice by demographic characteristics. Correlation between knowledge, attitude and practice was done using Spearman's rank correlation test. Binary logistic regression analyses were applied to identify possible determinants of good knowledge, attitude and practice. Results: A total of 521 completed questionnaires were included. The study revealed an overall good knowledge (16.09/20), attitude (8.34/10) and practice (12.73/14) scores. Education status, standard of living (rural/urban) and economic status determined an adequate overall knowledge, attitude and practice score, while an adequate practice score varied significantly by standard of living and education status. Significant positive linear correlations were found between knowledge-attitude (r = 0.513), knowledge-practice (r = 0.407) and attitude-practice (r = 0.407). Conclusion: The study demonstrated good overall knowledge, attitude and practices towards COVID-19 pandemic among gynaecological oncology OPD patients and their attendants. Supplementary Information: The online version contains supplementary material available at 10.1007/s40944-022-00624-1.

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.

Salvage (Re)radiation in Oligometastatic and Oligorecurrent Cervical Cancer.

PURPOSE: In patients with recurrent or metastatic cervical cancer, the median survival time is 13 to 24 months based on the choice of palliative systemic chemotherapy. Evolving evidence suggests that the addition of radiation may lead to improved survival. METHODS AND MATERIALS: Consecutive patients treated with radiation with or without systemic chemotherapy for oligometastatic or oligorecurrent disease within the period from 2017 to 2020 were included. All patients received systemic chemotherapy consultation and radiation to relapsed or metastatic sites. Progression-free survival (PFS) was determined as the period between diagnosis of relapse or metastasis and the last progression of the disease. Overall survival (OS) was defined as the time between the date of diagnosis of relapse or metastasis and follow-up or death. The effect of various prognostic and predictive factors was estimated using the Kaplan-Meier method and log-rank test. RESULTS: Fifty-eight consecutive patients were included. The median time to relapse was 18 months (8-205 months). At the time of first relapse, 34.4% of patients (n = 20) had locoregional relapse, 32.8% (n = 19) had distant nodal metastases, and 32.8% (n = 19) had visceral metastases. The relapse was within previously irradiated portals in 34.5% (n = 20), out of field in 50% (n = 29), and both in 15.5% (n = 9) of patients. Overall, 56% of patients (n = 33) received systemic chemotherapy. The radiation therapy dose in equivalent doses of 2 Gy at the time of retreatment was 44 Gy (31-68 Gy). The median PFS and OS from the date of first relapse were 16 (12-19) and 28 months (2-108), respectively. Grade ≥3 toxicity was observed in 19% of patients. No patient- or treatment-related factor was identified as predictive of OS on univariate analysis. CONCLUSIONS: The use of potentially radical doses of radiation, including reirradiation at locoregional or distant oligorelapse or metastasis, is associated with encouraging PFS and OS in patients with cervical cancer.

Months and Severity Score (MOSES) in a Phase III trial (PARCER): A new comprehensive method for reporting adverse events in oncology clinical trials.

Background: Adverse event reporting in oncology trials lacks temporal description. We propose a toxicity summarizing method that incorporates time. Methods: Patients recruited in a phase III trial (NCT01279135) that compared three-dimensional conformal radiotherapy (3DCRT) and intensity modulated radiotherapy (IMRT) for late toxicity in cervical cancer were included. Adverse events were reported using Common Terminology Criteria for Adverse Events (CTCAE) v3.0 and quality of life (QOL) with EORTC QLQ-C30 and CX24. A total of six symptoms with a related QOL question (diarrhoea, abdominal pain, anorexia, urinary incontinence, frequency and fatigue) were included. Month and severity score [MOSES= ∑ (CTCAE grade x proportionate time)] was calculated. Cumulative-MOSES (C-MOSES) was calculated by summating these 6 individual MOSES. QoL was categorized as "substantially symptomatic" or "not". Receiver operator curve analysis was performed to determine the MOSES cut off that predicts for substantial QOL symptoms. CTCAE and MOSES were tested for accurately categorizing QOL impact. Findings: In the construction dataset, 201/300 patients had symptoms. MOSES > 0.20 had higher accuracy than CTCAE for predicting impact on QOL related to diarrhoea (85% vs. 69%), anorexia (61% vs 51%), abdominal pain (71% vs. 57%), urinary incontinence (72% vs. 61%) and frequency (62% vs. 59%). C-MOSES > 0·70 correlated with reduction in role functioning and global QOL. While no difference was seen in CTCAE grade ≥1 Gastrointestinal (GI) toxicity between 3DCRT or IMRT arm, 3DCRT had higher C-MOSES than IMRT (HR=0.64;95% CI 0.41-0.99, p = 0.04). Interpretation: MOSES has higher accuracy than CTCAE in categorizing symptom specific and functional QOL. These results require further external validation. Funding: None.

Serial Bone Density Changes in Women Undergoing Pelvic (Chemo) Radiation: Results From the PARCER Trial.

PURPOSE: Pelvic irradiation leads to substantial dose to the pelvic girdle. However, bone density loss as a function of radiation therapy dose and time has not been investigated. This study was undertaken to evaluate such a dose-response relationship. METHODS AND MATERIALS: Women undergoing pelvic radiation therapy for cervix cancer within a phase 3 trial were included. The study necessitated 2 computed tomography imaging sets acquired at least 12 months apart in patients with no evidence of relapse. All images were transferred to the treatment planning system to determine radiation dose and Hounsfield unit (HU). Across the entire lumbopelvic region (lumbar 1-5 [L1-5] vertebrae, pubic symphysis, femur, acetabulum, greater trochanter, and anterior-superior iliac spine) multiple regions were defined to measure radiation therapy dose and HU. Bone health was categorized as normal if >130 HU, osteopenic at 110 to 130 HU, and osteoporotic <110 HU at baseline and follow-up. Univariate analysis was performed to test the effect of various factors on HU. Further interaction among radiation therapy dose, time, and HU was assessed using a linear mixed model. RESULTS: Overall, 132 of 300 patients were eligible. The median age was 49 (42-56) years. With a prescription dose of 50 Gy, the L1 and L2 vertebrae received a median dose of 1.2 and 4 Gy, respectively, and L3-5 received 10 to 50 Gy. At 24 months, median HU loss at L4-5 was 45 HU (interquartile range, 34-77 HU). Out of the 132 patients, at baseline 96% had normal bone health. However, at the last follow-up, 3% of patients had normal bone health, 12% developed osteopenia, and 85% developed osteoporosis (P < .001). There were no patient- or treatment-related factors predicted for HU loss on univariate analysis. HU loss >60 to 70 was observed at >45 Gy at L5 vertebra (60-70 HU, P < .02) and >15 Gy at L4 vertebra (33 HU; P = .04). CONCLUSIONS: Dose-response relationship is observed between radiation dose and bone mineral density loss. Prospective studies are needed to corroborate these observations and design future interventions.

Outcomes of Cervical Cancer in HIV-Positive Women Treated With Radiotherapy at a Tertiary Care Center in India.

PURPOSE: There are limited data on management of cervical cancer in women living with HIV in the modern antiretroviral therapy era. The study aimed to evaluate outcomes and toxicities of these patients treated with radiotherapy. MATERIALS AND METHODS: A retrospective analysis of HIV-positive cervical cancer patients treated with radiotherapy between 2011 and 2018 was conducted at a tertiary care center in India. RESULTS: Eighty-two HIV-positive cervical cancer patients treated with radiotherapy were identified. Their median age was 45 years. Seventy-four (90%) patients received radiotherapy with curative-intent and eight patients received palliative radiotherapy. Median CD4 count at the start of treatment was 342 cells/mm3 (interquartile range: 241-531). Among patients planned for definitive radiotherapy, concurrent cisplatin was planned in 52 (70%) patients with a median of four chemotherapy cycles, and 81% (n = 60) patients received brachytherapy. Among patients who received brachytherapy, the median prescription dose was 80 Gy. Seventy-seven patients completed their prescribed treatment. At a median follow-up of 37 months, 3-year disease-free survival of patients planned with curative-intent was 54%. On multivariate analysis, treatment completion was associated with favorable disease-free survival. Grade III/IV acute gastrointestinal toxicity was seen in five (6.8%) patients, whereas 30% patients had grade III/IV acute hematologic toxicity. All these patients completed their planned radiotherapy with good supportive care. CONCLUSION: Standard treatment of chemoradiation should be planned in women living with HIV with well-managed HIV presenting with locally advanced cervical cancer. Our study highlights the need for optimal management of these patients by a multidisciplinary team with intensive supportive care to ensure completion of planned treatment to achieve better outcomes.

Telemedicine and cancer care in India: promises, opportunities and caveats.

Telemedicine has revolutionized areas of medical practice and care. It has a potential in field of continuum of cancer care in India. SARS-CoV-2 has highlighted the potential use of this tool effectively. Scope of newer applications of telemedicine in field of cancer is reviewed in current paper enlisting benefits to patient, healthcare providers and centers in a developing country like India. Each of them is supported by appropriate evidence and examples. An analysis of strengths and opportunities when compared with weakness and threats brings out how telemedicine can redistribute oncology work force in a rational way and minimize disruption caused by the pandemic. Telemedicine can be utilized in cancer management starting from prevention, screening, diagnosis, treatment and rehabilitation to palliative care.

Specialists working for decades in the field of oncology are the best persons to endorse telemedicine, as they can leverage its use to its full potential. The present article is a rigorous review of past literature on telemedicine as well as proposed uses of technologies based on experiences of the authors. It will strengthen promotive, preventive, curative and rehabilitative healthcare delivery.

Clinical outcomes of patients treated with template-based high-dose-rate interstitial brachytherapy boost for post-operative recurrent gynecological malignancies: A retrospective analysis.

Purpose: To report the clinical outcomes in patients treated with Martinez universal perineal interstitial template (MUPIT)-based interstitial brachytherapy boost for primary and recurrent vault and vaginal cancers, and to perform a comparative analysis with our previously published series of similar patients. Material and methods: One hundred and seventeen patients treated between January, 2009 and December, 2015 were evaluated. Descriptive statistics for the patterns of relapse, local recurrence-free survival (LRFS), disease-free survival (DFS), overall survival (OS), and late toxicities were carried out. Kaplan-Meier curves were used for survival analysis. All variables with the potential to affect outcomes were tested using log-rank test for statistical significance. Results: At a median follow-up of 63 months, LRFS, DFS, and OS at 3/5 years were 77.1%/74.7%, 61%/52%, and 72.3%/63.1%, respectively. Overall treatment time (OTT) of 56 days did not affect outcomes. Bulky tumors and OTT > 63 days adversely affected LRFS. Overall treatment time also significantly impacted DFS and OS. Grade 3-4 late bladder toxicities were observed in 1.7% patients, and grade 3-4 late rectal toxicities in 5% patients. Compared to our previous series, the outcome in the current series is better in terms of severe late toxicities (5% improvement in rectal toxicity, and 2.7% improvement in bladder toxicity) and OS by 10%. This could be attributed to the increasing use of concurrent chemotherapy and relative optimization strategies for organs at risk. Conclusions: Patients with primary and recurrent vault and vaginal cancers treated with high-dose-rate interstitial brachytherapy boost using MUPIT resulted in modest clinical outcomes and acceptable late toxicities. OTT was the most important factor affecting the outcomes.