Anjana JoelContext Patients with seminoma present with advanced disease. End-of-treatment (EOT) positron emission tomography-computed tomography (PET-CT) is done to assess response and direct management of post-chemotherapy residual masses. Purpose This article assesses the utility of EOT PET-CT in the management of post-chemotherapy residual lymph nodal masses seminoma. Materials and Methods We analyzed all patients with seminoma who underwent an EOT PET-CT from January 2015 to January 2020 at our center and calculated the positive predictive value (PPV) and negative predictive value (NPV) of EOT PET-CT in the entire cohort of patients and among subgroups. Results A total of 34 male patients underwent EOT PET-CT. Fourteen (41.2%) were stratified as good risk and 20 (58.8%) as intermediate risk. The median follow-up was 23 months (interquartile range: 9.75-53 months). In 23 patients there were residual masses of size more than 3 cm at the EOT PET scan. EOT PET was positive as per the SEMPET criteria in 18 (78%) out of 23 patients. None underwent retroperitoneal lymph node dissection. All four who underwent image-guided biopsy, showed only necrosis on pathology. One patient with positive mediastinal node (standardized uptake value 13.6) had granulomatous inflammation. There was no relapse or progression during this period of follow-up. The NPV for EOT PET-CT for the entire cohort, > 3 cm, and > 6 weeks cutoff were 100%, respectively. The PPV for EOT PET-CT for the entire cohort, > 3 cm residual mass, and > 6 weeks cutoff were 8.7, 11.11, and 6.67%, respectively. Conclusion EOT PET-CT has a low PPV and high NPV in predicting viable tumor in post-chemotherapy residual masses among patients with seminomatous germ cell tumors. If required, EOT PET positivity can be confirmed by a biopsy or reassessed with a repeat PET-CT imaging to document persistent disease prior to further intervention.
Abstract Human epidermal growth factor receptor 2 (HER2)-positive is an aggressive subtype of breast cancer and has historically been associated with poor outcomes. The availability of various anti-HER2 therapies, including trastuzumab, lapatinib, pertuzumab, and trastuzumab emtansine (TDM-1), has remarkably improved the clinical outcomes in patients with HER2-positive metastatic breast cancer (mBC). However, there is a need to optimize treatment within this population, given the wide variability in clinical presentation. Additionally, geographical and socio-economic considerations too need to be taken into account. To clarify and collate evidence pertaining to HER2-positive metastatic breast cancer, a panel of medical and clinical oncologists from across India developed representative clinical scenarios commonly encountered in clinical practice in the country. This was followed by two meetings wherein each clinical scenario was discussed in detail and relevant evidence appraised. The result of this process is presented in this manuscript as evidence followed by therapeutic recommendations of this panel for management of HER2-positive mBC in the Indian population.
Response to neoadjuvant chemotherapy is associated with improved outcomes for patients with triple negative breast cancer (TNBC). Patients with residual disease are at increased risk of relapse and death from breast cancer. In this retrospective study, we aimed to evaluate the efficacy and safety of cisplatin added to standard neoadjuvant chemotherapy for locally advanced TNBC.All TNBC treated with neoadjuvant cisplatin 60mg/m2 once in 3 weeks with weekly paclitaxel for 12 weeks, following 8 weeks of dose-dense epirubicin 90mg/m2 or doxorubicin 60mg/m2 with cyclophosphamide 600mg/m2 were analyzed retrospectively. The data related to pathological complete response, adherence to planned therapy, disease-free survival and overall survival were collected.Eighty-three patients were included, of whom 80% had stage III disease. Pathological complete response in both breast (T0/Tis) and axilla (N0) was observed in 48.1% of patients. Miller Payne grade 5 pathological response in the breast was seen in 61% of patients. Good partial responses (Miller Payne grades 3,4) were observed in 32.5% of patients. The remaining 6.5% were poor responders. Seventy-seven patients underwent surgery. The disease-free survival at 1 and 3 years for those who had a pathological complete response was 96.7% and 77.6%, respectively, and 92.3% and 62.7% for those who did not, respectively. The predominant adverse events were hematological, with anemia being the most common one.The addition of cisplatin to neoadjuvant chemotherapy with anthracycline and taxane in TNBC was tolerable and produced a high rate of pathological complete response. Cisplatin added to standard chemotherapy in patients with locally advanced TNBC could improve clinical outcomes.
Abstract Purpose In a developing country like India, genomic data sets for even the most clinically relevant genes like BRCA1 and BRCA2 is rather scarce. Also, there is a need to identify and screen population specific BRCA hotspots to pave a way for affordable genetic testing strategies in clinical practice. Method This is an ambispective study to evaluate an NGS based approach to identify pathogenic variants in BRCA1 and BRCA2 genes among 430 patients with Breast and Ovarian cancers. The target enrichment was carried out using the in-house designed Multiplex-PCR followed by targeted Next-generation sequencing (NGS) for BRCA1 and BRCA2 . Also, allele-specific PCR based genotyping of del185AG was carried out in additional 120 patients. Results In this study, we have identified 100 BRCA1 and BRCA2 variants and based on ACMG 2015 guidelines, these variants were classified as 46 pathogenic, 9 likely pathogenic, and 45 VUS. Of these variants, three were novel, two with likely pathogenic, and one variant of uncertain significance (VUS). The 185delAG was identified as a recurrent mutation in the Southern Indian population accounting for 25.45% of the pathogenic variants. In addition, a family history of cancers of the breast, ovary, pancreas, or prostate (BOPP) was found to be associated with a higher risk of identifying a deleterious BRCA1/2 variant [OR 3.2 (95%CI 1.84–5.77) p ≤ 0.001]. Conclusions These results suggest that Multiplex PCR-NGS is a sensitive and specific strategy for BRCA testing. However, ASPCR-based genotyping of BRCA1 (NM_007300.4): c.68_69del followed by targeted NGS would be a cost-effective approach in south Indian patients.
Cancer can have profound social and economic consequences for people in India, often leading to family impoverishment and societal inequity. Reported age-adjusted incidence rates for cancer are still quite low in the demographically young country. Slightly more than 1 million new cases of cancer are diagnosed every year in a population of 1·2 billion. In age-adjusted terms this represents a combined male and female incidence of about a quarter of that recorded in western Europe. However, an estimated 600 000–700 000 deaths in India were caused by cancer in 2012. In age-standardised terms this fi gure is close to the mortality burden seen in high-income countries. Such fi gures are partly indicative of low rates of early-stage detection and poor treatment outcomes. Many cancer cases in India are associated with tobacco use, infections, and other avoidable causes. Social factors, especially inequalities, are major determinants of India’s cancer burden, with poorer people more likely to die from cancer before the age of 70 years than those who are more affl uent. In this fi rst of three papers, we examine the complex epidemiology of cancer, the future burden, and the dominant sociopolitical themes relating to cancer in India.
Abstract We assessed the efficacy, tolerability, and cost-effectiveness of a novel neoadjuvant regimen comprising docetaxel-cyclophosphamide alternating with epirubicin-cisplatin (ddDCEP) administered biweekly for 16 weeks in 116 patients with early triple-negative breast cancer. This regimen achieved a high pathological complete response (ypT0/TisN0) rate of 55.2% and favorable survival outcomes (30-month event-free survival, 91.2%; overall survival, 97%). Febrile neutropenia was observed in 4.3% of patients, and 98% completed at least six of eight cycles. ddDCEP was more cost-effective than contemporary carboplatin-based regimens. This novel approach offers an economically viable and effective alternative to current chemoimmunotherapy regimens, and merits further investigation
Abstract PURPOSE Preoperative long course chemoradiation (LCCRT) followed by total mesolectal excision (TME) results in excellent local control but distant failure rates remain high. Total neoadjuvant therapy (TNT) with pre-operative delivery of systemic chemotherapy and chemoradiotherapy results in a higher pathological response, improved event free and overall survival and is becoming the new standard of care. We describe our experience with a hybrid TNT consisting of induction chemotherapy followed by chemoradiotherapy using full dose 5FU without oxaliplatin. METHODS In this single center study, adults with a LARC were included. Patients were eligible if they were aged 18 years or older, with an Eastern Cooperative Oncology Group (ECOG) performance status of 0–1, biopsy-proven, newly diagnosed LARC, which was classified as high risk on pelvic MRI (with at least one of the following criteria: clinical tumor [cT] stage cT4a or cT4b, extramural vascular invasion (EMVI), clinical nodal [cN] stage cN2, mesorectal fascia involvement and enlargement/tumor deposits on lateral lymph nodes). The hybrid TNT protocol comprised of six biweekly courses of modified FOLFOX6 (m FOLFOX6) followed by addition of pelvic LCCRT with four concurrent cycles of biweekly 5-FU 2600 mg/m2 + LV 200 mg/m2 without oxaliplatin to complete uninterrupted 20 weeks of full dose 5FU + LV chemotherapy. Pelvic chemoradiotherapy consisted of 28 daily fractions of 2 Gy up to 50.4-54Gy including boost to extra-mesorectal nodes. Surgery was planned 11-13 weeks after completing chemoradiotherapy. Outcomes of interest were pathological complete response (pCR), 2 year disease free survival (DFS) and overall survival (OS). RESULTS Between July 2017 to August 2020, 84 adults, predominantly male (65.5%) aged 42.5±13 years with LARC were treated with the TNT protocol. High risk features were T3/T4 in 80 (95.3%), N2 nodes 51(60.7%), signet ring cell histology 22(26.2%), meso-rectal fascia involvement 73(86.9%), EMVI 54 (64.3%) and lateral pelvic nodes 25(29.8%). Eighty- one (96.4%) completed all planned chemotherapy. All but two patients completed the planned RT. pCR was noted in 27 (32%). Twenty-five (29%) did not undergo surgery- 6(7%) opted for non-operative management (NOM) after complete clinical response (cCR), 5 refused surgery, 13(15.4%) were deemed inoperable due to inadequate tumor regression despite TNT (R0 resection was not feasible) and 2 did not complete treatment. Grade 3 &4 toxicities included neutropenia in 20 (23.8%), diarrhea in 12 (14.2%) and anemia in 9(10.7%) patients. Grade 5 toxicities were seen in one patient who died from neutropenic sepsis, and another who developed a cerebrovascular accident on therapy. After 24.5 months of median follow-up, 23 (27%) patients recurred, with local recurrence in 5(6%), systemic recurrence in 16 (19%) and both in 2(2.4%). The median disease-free survival (DFS) of the whole cohort was 22.5 months. Those who did not undergo surgery(n=19) despite residual disease (no cCR) had the worst outcomes (mDFS 11.4 months versus 27.7months, p=<0.0001 and mOS 15 months versus 29.2 months p=<0.0001). CONCLUSION The hybrid TNT regimen was administered without significant dose delays or interruptions. Toxicity was manageable but with two treatment related deaths. pCR of 32% is comparable to contemporary trials, however the 2-year recurrence rates were not improved. Ability to undergo surgery after TNT predicted for improved DFS and OS.
Abstract Background Triple-negative breast cancer (TNBC) with residual disease post chemotherapy, have increased chance of relapse and lower survival with varying degree of pathological complete response (pCR) after neoadjuvant chemotherapy (NAC). However, the risk of recurrence is high among those who do not achieve pCR and characterizing the mutational landscape of this fairly heterogeneous subset of patients might provide some valuable insights. Methods The archival paired (pre- and post-NAC) samples of 25 patients with histopathologically confirmed TNBC with residual disease who received anthracycline-taxane as NAC, were processed by next-generation sequencing using a 72-gene panel. Somatic mutations were identified using UMI corrected .clc pipeline; gene annotation of the variants performed using VeP program. Data was analysed using IBM SPSS Statistics v23 and R v4.1.2 (RStudio 2021.09.1). The K-means algorithm was used to classify the samples into k number of clusters. Results Among all 50 tumour samples, a median of 12 mutations (IQR 7-17.25) per sample was observed. Missense mutations accounted for the overwhelming majority (73.5%). The predominant mutations in the pre-NAC samples were TP53(80%), PMS2(64%), PTEN(64%), ERBB2(48%), NOTCH1(44%) while the mutational profile was slightly different among the post-NAC samples: TP53(84%), AR(60%), PTEN(60%), PMS2(44%), ERBB2(40%). The burden of mutations did not differ among patients who received platinum or not (12.8 ± 6.9 Vs 11.25 ± 4.9; p-value 0.94), though there were several private mutations in the former group. Similarly, the tumor mutation burden was not very different among those with (n = 5) and without recurrence (14 ± 7.2 Vs 12.2 ± 6.6; p-value 0.49). The K-means clustering demonstrated two clusters -all patients with recurrence, except one, in the larger cluster. Conclusions The burden of mutations among the pre- and post-NAC samples mostly remained the same, although, mutations in specific genes for example- increase in mutations in the AR gene post-NAC, was noted. TP53 mutations predominated pre- and post-NAC. There was no significant difference in mutational burden and there were no recurrent / co-occurring mutations among those who received platinum therapy after NAC or among those with recurrence. The data throws significant light on the somatic mutational load, spectrum and heterogeneity, among TNBCs with residual disease.
'%3e%3ccircle r='20' fill='%23008'/%3e%3ccircle r='17.5' fill='%23fff'/%3e%3ccircle r='3.5' fill='%23008'/%3e%3cg id='d'%3e%3cg id='c'%3e%3cg id='b'%3e%3cg id='a' fill='%23008'%3e%3ccircle r='.875' transform='rotate(7.5 -8.75 133.5)'/%3e%3cpath d='M0 17.5.6 7 0 2l-.6 5L0 17.5z'/%3e%3c/g%3e%3cuse xlink:href='%23a' transform='rotate(15)'/%3e%3c/g%3e%3cuse xlink:href='%23b' transform='rotate(30)'/%3e%3c/g%3e%3cuse xlink:href='%23c' transform='rotate(60)'/%3e%3c/g%3e%3cuse xlink:href='%23d' transform='rotate(120)'/%3e%3cuse xlink:href='%23d' transform='rotate(-120)'/%3e%3c/g%3e%3c/svg%3e)
