Background: Neoadjuvant chemotherapy response rates in locally advanced breast cancer (LABC) vary significantly among Indian patients, and the factors affecting pathological complete response (pCR) rate are not clear in this population. Objectives: This study was aimed at identifying the various clinicopathological features associated with achieving pCR and its effect on disease-free survival (DFS) and overall survival (OS) among Indian women diagnosed with LABC. Materials and Methods: Women diagnosed with LABC between 2013 and 2019 and who received neoadjuvant chemotherapy followed by surgery and radiotherapy were ambispectively analyzed for clinicopathological responses and survival outcomes. Factors associated with pCR and the role of pCR as a prognostic factor for survival outcomes were examined. Results: After neoadjuvant chemotherapy, pCR was achieved in 99 (23.3%) patients, with the highest rates noted in patients with triple-negative breast cancer (TNBC) and human epidermal growth factor receptor 2 (HER2)-positive tumors. Compared to hormone receptor-positive tumors with HER2-negative status, all other tumor groups had significantly higher odds of achieving pCR after neoadjuvant chemotherapy (TNBC: adjusted odds ratio [aOR], 4.58 [95% CI, 2.20–9.53]; hormone receptor- and HER2+: aOR, 3.93 [95% CI, 1.66–9.27]; hormone receptor + and HER2+: aOR, 2.78 [95% CI, 1.20–6.44]). Hormone receptor status and attainment of a pCR after neoadjuvant chemotherapy were associated with better DFS and OS outcomes particularly in patients with HER2-positive and TNBC tumors. Conclusions: Patients who attain a pCR following neoadjuvant chemotherapy have improved survival outcomes; pCR rates vary by hormone and HER2 receptor status. Therapeutic approaches such as anti-HER2 and platinum-based regimens may be considered for achieving better pCR rates. The use of biomarkers for the identification of individuals with breast cancer who will not benefit from neoadjuvant chemotherapy should be considered along with early cancer detection strategies.

Background: The profile of patients with malignant melanoma in Asian countries is distinctly disparate from that of those in Western countries. Malignant melanoma is a rare malignancy with scarce literature from India. Objectives: We aimed to describe the clinical profiles and outcomes of Indian patients with advanced malignant melanoma. Materials and Methods: We retrospectively analyzed the data of consecutive patients with malignant melanoma who presented to the bone and soft tissue sarcoma clinic at the All India Institute of Medical Sciences, New Delhi, between January 2016 and March 2019. Our primary endpoint was to evaluate the clinical profile of the patients and the patterns of treatment. The secondary endpoints were response rate, progression-free survival (PFS), and overall survival (OS). Results: We included 93 patients in the cohort, with a median age of 53 years (range, 25–85). The majority of patients were men (61.3%); almost half had an Eastern Cooperative Oncology Group performance status of 2 or greater. Most (89.2%) patients had metastases at presentation. The most common primary sites were anorectal (24.7%), acral (24.7%), ocular (17.2%), head and neck (15.1%), and thigh (9.7%). The median number of metastatic sites at presentation was 2, with the most common sites of metastases being the lymph nodes (57%), lung (48.3%), liver (35.5%), and bone (25.8%). BRAF V600E mutation was present in three out of four tested patients, while c-KIT mutation was present in two out of seven tested patients. At a median follow-up of 18 months, the median PFS was 2 months (95% confidence interval, 1.2–2.7 months) and median OS was 7 months. Conclusion: Acral/mucosal melanoma is the most common melanoma among Indians and has poor outcomes. Limited access of patients with melanoma to standard-of-care therapeutic options remains an important issue in a resource-constrained country like India.

Background: Examination of the bone marrow on day 14 of induction chemotherapy for acute myeloid leukemia (AML) is a common practice. However, the evidence for re-inducing the patient based on early bone marrow response is limited. Objectives: This study was aimed at assessing the utility of bone marrow examination on day 14 of AML induction in predicting complete remission (CR) or residual disease and its impact on clinical decisions on re-induction in a resource-limited setting. Materials and Methods: This retrospective study was conducted at the Malabar Cancer Center, a tertiary cancer center in Kerala, India. Adult patients with AML who received 3 + 7 (daunorubicin + cytarabine) induction chemotherapy from January 2011 to December 2018 and underwent an early bone marrow examination on day 14 were included in the study. Early marrow response was considered adequate if the marrow cellularity was less than 15%–20%, with less than 5%–10% blasts. Patients with inadequate bone marrow response were given re-induction chemotherapy, if eligible. Unfit patients were continued on supportive measures. The end-of-induction bone marrow was done on day 28 after count recovery. Case records of all patients were reviewed, and data including the baseline characteristics, day 14 bone marrow response, and post-induction marrow status were collected. Results: Of the 96 patients who received induction chemotherapy during the study period, 78 underwent day 14 bone marrow assessment. The median age was 44 years (range, 15-66), and 43% of the patients were males. On day 14, 57 (73%) patients had adequate bone marrow response, 19 (24%) had inadequate response, and 2 (3%) had inconclusive results. Among the patients with inadequate responses, 12 attained CR at the end of induction, although only 9 received re-induction. Adequate day 14 bone marrow had a sensitivity of 89.8% (95% confidence interval [CI], 79–96) in predicting the remission status at the end of induction. The specificity of inadequate day 14 marrow response in predicting residual disease in post-induction bone marrow was 89% (95% CI, 79–96). Similarly, the positive predictive value was 100% and the negative predictive value was 14%. Conclusion: Although assessment of day 14 bone marrow response is useful in predicting the chances of CR at the end of induction, its role in guiding the decision for re-induction is doubtful, and larger studies are needed to address this question.

Background: Ramucirumab plus docetaxel has been shown to improve survival as a second-line treatment for patients with Stage IV non-small-cell lung cancer (NSCLC) in the multicenter, double-blind, randomized, Phase III trial, REVEL. Objective: In this exploratory analysis, we aimed to assess the safety and efficacy of ramucirumab plus docetaxel in the Indian patient subgroup of the REVEL study. Materials and Methods: Adult patients with histologically or cytologically confirmed NSCLC of either squamous or non-squamous histology, who progressed during or after first-line platinum-based chemotherapy were randomized to receive either ramucirumab plus docetaxel or placebo plus docetaxel. We performed a descriptive analysis of the baseline characteristics, safety, and efficacy of the Indian subgroup of the overall REVEL study (NCT01168973). The analyses presented here are not intended for comparison purposes either between treatment arms or to the overall REVEL study. Results: Fifty-five Indian patients were included in the REVEL study. Baseline characteristics and prior therapies of these patients were well-balanced between the treatment arms. Almost 80% patients had non-squamous histology, and 78.2% were men. All patients had received prior standard platinum-based therapy: 25.5% of patients received maintenance, while 18.2% received taxane (paclitaxel only) as part of their first-line therapy. The incidence of treatment-emergent adverse events regardless of grade was similar between the two arms in the Indian safety subgroup. Patients treated with ramucirumab plus docetaxel experienced a median overall survival (OS) of 13.5 months (95% confidence interval [CI], 5.7–17.6) and progression-free survival (PFS) of 5.6 months (95% CI, 2.8–7.0) relative to a median OS of 5.3 months (95% CI: 3.6–9.9) and PFS of 1.5 months (95% CI: 1.3–5.2), for those treated with placebo plus docetaxel. Conclusion: In this exploratory analysis, Indian patients enrolled in the REVEL study demonstrated prolonged OS and PFS when treated with ramucirumab plus docetaxel, consistent with the overall results of the REVEL study. Ramucirumab plus docetaxel appears to be well tolerated by Indian patients, as the rates for most adverse events were similar with and without ramucirumab.

Background: Large number of screen failures in trials often result in delayed drug approvals, an increase in the financial burden for conducting research, and limit the applicability of the study results to patients in the clinic. Objectives: This post hoc analysis was aimed at assessing the reasons for screen failures in a phase III, investigator-initiated clinical trial conducted in India. Materials and Methods: The study was conducted at the Tata Memorial Center, a tertiary cancer center in Mumbai, India. We maintained a log of all potential study candidates who underwent screening in our outpatient department between May 2016 and January 2020. This included the name of the study subject, hospital registration number, age, and sex. We also recorded the screening date and outcome of the screening process (whether enrolled in the study and if not, the reason for it) along with the number of patients who were finally randomized in the study. We evaluated factors that may have impacted screen failure including age, sex, and performance status (PS). Results: A total of 594 patients were screened. Of these, 422 were enrolled and 172 failed screening. Out of the 172 patients who were not enrolled, 105 (61%) did not meet the eligibility criteria and 67 (39%) refused to participate due to various reasons. The reasons for non-enrollment in the trial included the lack of a place to stay in Mumbai (35, 20.3%), patient wanted only a particular therapy (16, 9.3%), age over 70 years (15, 8.7%), poor PS (4, 2.3%), deranged organ function (13, 7.6%), active tuberculosis (2, 1.2%), primary tumor in the nasopharynx/thyroid/salivary gland/unknown primary (31, 18%), positivity for viral markers of infection (12, 7%), platinum-refractory disease (23, 13.4%), unwillingness to participate in research (15, 8.7%), patient not willing as they were not accompanied by a relative=1(0.06%) and other reasons (5, 2.9%). Age over 60 years (P = 0.001), and poor PS (P < 0.001) significantly increased the screen failure rate. Conclusion: The most common cause for screen failures is the nonfulfillment of the eligibility criteria, followed by patient-related reasons such as unavailability of a place to stay at the trial location. Broadening the eligibility criteria to better reflect the patients most commonly seen in the clinic will function both to decrease the rate of screen failures and increase the applicability of the study results.

Background: Carcinoma of the esophagus and gastroesophageal junction is an aggressive disease with limited survival. Standard management consists of multimodality therapy, incorporating chemotherapy, radiation, and surgery. Objectives: We aimed to understand the obstacles in treating patients with resectable esophageal cancer with neoadjuvant chemoradiotherapy followed by surgery. We also assessed the disease outcomes in the patients who completed surgery. Materials and Methods: We included patients with resectable esophageal carcinoma who received neoadjuvant chemoradiation between March 2017 and August 2019 at the Homi Bhabha Cancer Hospital in Sangrur, Punjab, a tertiary care center in rural India. As surgery for esophageal cancer was not performed at our center, patients had to be referred to a higher center for this. Patients were divided into two groups, based on the therapy they received following neoadjuvant chemoradiation: those who completed surgery (Group A) and those who did not (Group B). The pathologic response rates were noted. The disease-free survival (DFS) and overall survival (OS) were compared between the two groups. Results: A total of 55 patients (32 in Group A and 23 in Group B) were included the study. In Group A, complete pathologic responses were noted in 19 (59.4%), partial responses in 11 (34.4%) and poor responses in 2 (6.2%) patients. The major reasons for not undergoing surgery were patient refusal as they were feeling better after chemoradiation (8, 34.8%) and the presence of advanced inoperable (5, 21.7%) or metastatic disease (3, 13%) on imaging after chemoradiation. The median DFS in Group A and Group B was 8 months (range, 0–38 months) and 14 months (range, 0–29 months), respectively, and the 2-year DFS was 57.8% and 73.3%, respectively (P = 0.28). Median OS in Group A and Group B was 17 months (range, 3–43 months) and 17 months (range, 2–31 months), respectively, and the 2-year OS was 52.6% and 53.5%, respectively (P = 0.70). Conclusions: Implementing neoadjuvant chemoradiation followed by surgery for resectable esophageal cancer in a center where esophageal cancer surgery cannot be performed is challenging. Among patients who undergo surgery following neoadjuvant chemoradiation, complete pathologic responses occur in 59.4% patients, and clinical outcomes appear to be similar to those reported in the literature.

Background: Technology has advanced tremendously and can address the gaps in the care of older adults with cancer. Studies from high-income countries reveal that the use of technology among older adults is on the rise, but there are no published data regarding the use of technology by health-seeking older adults from India. Objectives: We aimed to assess the use of mobile phones, Internet, and social media applications among older adults with cancer attending a geriatric oncology clinic. We also aimed to study their association with various intrinsic factors. Materials and Methods: This cross-sectional study was conducted in the geriatric oncology clinic at the Tata Memorial Hospital, a tertiary care center in Mumbai, India, between April 2021 and October 2021. Participants were patients with cancer aged 60 years and over, who were referred to the geriatric oncology clinic. Clinicodemographic details were recorded, and a multi-dimensional geriatric assessment was performed. Patients were asked whether they owned and used mobile phones, Internet, E-mail, and social media applications such as WhatsApp and Facebook. The same questions regarding technology use were asked to their accompanying caregivers. Categorical variables were compared using the Fisher's exact and Pearson's Chi-squared test. Results: A total of 309 participants were included. The median age was 68 (interquartile range, 64–72) years; 262 (85%) participants were aged <75 years. There were 234 (76%) men in the cohort. A total of 25 (33%) women and 25 (11%) men were uneducated; 225 (81%) participants had mobile phones; and 24 (9%) had mobile phones and landlines. Female patients (59% vs. 77%, P = 0.001) and those with poor vision (67% vs. 80%, P = 0.036), no education (50% vs. 74%, P < 0.001), and impaired cognition (49% vs. 84%, P < 0.001) were less likely to own a mobile phone. A total of 70 (25%) participants reported that they accessed the Internet, but only 16 (6%) used Internet, E-mail, and social media on their own phones. Use of the Internet and social media was less likely among people with no education ([4% vs. 22%, P < 0.001] and [6% vs. 21%, P < 0.01], respectively) and impaired cognition ([5% vs. 26%, P = 0.013] and [8% vs. 28%, P = 0.022], respectively). Among accompanying caregivers, 297 (99%) reported that they used mobile phones, while 223 (75%) used E-mail and social media applications. Conclusion: Over 80% of older Indian adults with cancer use mobile phones, but only 25% use Internet and social media. Women and those with no education, poor vision, and impaired cognition are less likely to own a mobile phone. People with no education and impaired cognition are also less likely to use Internet and social media. Further studies are required to understand the acceptance rate and feasibility of technology use in our setting and to gather more evidence for the effectiveness of these interventions.

The evolution of therapeutics for triple-negative-breast cancer (TNBC) has been lagging behind in comparison to that of other breast cancer subtypes. This review focuses on the recent developments with the potential to change future clinical practice. We searched the PubMed database for randomized trials on TNBC published in the past 2 years using the key term, “Triple-negative breast cancer.” Abstracts and outcomes of various studies presented at major oncology meetings were also assessed. A total of 54 studies were included in this review. Recent advances in molecular studies have delineated several cellular alterations revealing various targetable biomarkers. In addition, immunotherapeutic agents are being explored in the neoadjuvant setting and have shown major improvements in pathological complete response. Poly-adenosine diphosphate ribose polymerase inhibitors (PARPi) have transformed the management of TNBC, especially breast cancer gene-1/2 (BRCA1/2)-mutant and homologous recombination repair-deficient tumors. PARPi are now being utilized in the neoadjuvant setting, for maintenance following definitive treatment, and in metastatic disease. Sacituzumab govitecan has demonstrated improved outcomes in relapsed/refractory metastatic TNBC and has been approved for this indication. Capivasertib and ipatasertib have demonstrated promising results in patients harboring alterations in the phosphatidylinositol-3-kinase (PI3K)/protein kinase B pathway.

Preoperative imaging is essential for staging carcinomas of the oral tongue in addition to clinical staging. The current TNM staging of the oral cavity according to the 8^th edition of the American Joint Committee on Cancer is appropriate for buccal mucosal carcinomas due to their proximity to and frequent involvement of the skin, bone, and masticator space in case of advanced disease. However, it is inadequate for the subclassification of tongue carcinomas. Tongue cancers, even those in the advanced stage, do not frequently involve these structures, thus leading to understaging of these tumors. We observed that the preoperative radiological markers such as perineural invasion, hyoid bone involvement, extrinsic muscle involvement up to their origin, and distance of the paralingual septum from the tumor are better predictors of prognosis of carcinoma of the tongue. In this article, we review the existing literature on T4 staging of tongue carcinomas and also propose a few modifications to the current staging system from a radiological perspective. A comprehensive search of abstracts of prognostic markers in tongue carcinoma and their impact on T4 stage was done. The PubMed and the Cochrane library were used. The keywords for Medical Subject Headings were as follows: Magnetic resonance imaging, Neurovascular bundle, Oral tongue, Perineural invasion, Squamous cell carcinoma, Extrinsic muscle invasion, Hyoid bone involvement, and Paralingual septum distance. The reference lists of included studies and review articles were checked manually. Unpublished data were not included in this review. We suggest a radiological T4 staging system which is more suitable for staging tongue cancers.

The goal of this systematic review was to describe the use of augmented reality and virtual reality in cigarette smoking cessation and the adherence to smoking cessation among smokers. We searched several databases to identify suitable studies published between September 2011 and September 2021 for inclusion in this review. Suitable MeSH terms were used to devise a precise search strategy using PubMed, Google Scholar, Cochrane Library, and Turning Research into Practice database. The search yielded 304 articles, of which 5 were selected and 4 were considered for quality assessment. All four studies suggested that when the intervention was given through virtual reality, the adherence to smoking cessation was apparently high. Promoting cigarette cessation through conventional techniques could take a longer time for achieving commitment among those who wished to quit, while virtual reality created an interest to quit smoking. Arranging for augmented and virtual reality experiences for smokers through mobile applications and virtual reality headsets in the future could help improve smoking cessation and adherence compared to conventional pamphlets for health education.

Reflex testing for the T790M mutation is important in patients with non-small cell lung cancer (NSCLC) who progress on first- or second-generation tyrosine kinase inhibitors (TKIs). Reflex testing, initiated by the treating medical oncologist, allows for the faster identification of patients who are eligible to receive a third-generation TKI such as osimertinib, which is the only TKI to report favorable outcomes in patients with T790M mutation. International guidelines and the Indian consensus guidelines recommend tissue rebiopsy as the gold standard to source genetic material for the testing of molecular biomarkers. As a result of its non-invasiveness, although liquid profiling is currently preferred as a starting point for diagnosing T790M mutations, in the case of inconclusive results, repeat tissue biopsy and reflex tissue-based T790M testing are deemed essential because of higher diagnostic certainty. Medical oncologists along with interventional radiologists and pathologists play a critical role in ensuring the feasibility of repeat tissue biopsy in patients with advanced NSCLC. Reflex tissue testing has the potential to identify acquired T790M mutation in patients with lung cancer at progression. We conducted a literature search in Embase and PubMed for the relevant articles to be included in this review. We also referred to the international and local guidelines to develop the testing algorithm. This narrative review provides a practical algorithm for reflex tissue testing and explains the significance of tissue rebiopsy in improving treatment outcomes in patients with NSCLC post-disease progression.

The advent of stratified medicine and tailored therapies has caused non-small cell lung cancer (NSCLC) to become a subject of keen interest, with an emphasis on comprehensive genomic testing for driver mutations and biomarkers. The rearranged during transfection (RET) gene rearrangement has been observed in 1%–2% of all NSCLCs. In this edition of the biomarker series, we have reviewed the available literature on RET and its biology, along with the clinical features and therapeutic options for RET-rearranged NSCLC. For the purpose of this review, we performed a detailed search of the PubMed, Scopus, and My Cancer Genome databases using the keywords “RET,” “NSCLC,” “pralsetinib,” and “selpercatinib.” We included 42 articles in the final review. Studies suggest that RET rearrangement has emerged as a new biomarker of interest in NSCLC owing to the development and approval of selective RET inhibitors. Newer trials comparing RET inhibitors with chemotherapy and immune checkpoint inhibitors are underway. However, more studies are required to lucidly explain the underlying biology, including newer mechanisms of resistance to selective RET inhibitors, to guide drug development in future.

The discovery and clinical efficacy of imatinib in chronic myeloid leukemia opened a new and interesting avenue of oral small-molecule tyrosine kinase inhibitors. Thereafter, several such molecules with efficacy across multiple tumor types have been discovered. One of the oral multi-kinase inhibitors is lenvatinib, which started its journey in 2008 when it showed efficacy on stem cells in the laboratory setting and was first approved by the United States Food and Drug Administration in August 2015 for the management of radioiodine-refractory differentiated thyroid cancer. Since then, it has been approved for hepatocellular, endometrial, and renal cell carcinomas, and many more trials are underway for lenvatinib in multiple solid tumors, either alone or in combination with immunotherapy. In addition to the robust data on the efficacy of this drug, it is known for its tolerability with different dosing schedules in different tumor types, a feature unique to this drug. Therefore, an in-depth understanding of its mechanism of action, pharmacokinetics, pharmacodynamics, dosage in different tumor types, expected side effects, and predictors of response will go a long way in its safe and appropriate use in the clinics. In this review, we aim to summarize and collate these data in a reader-friendly manner, thus making it a ready reckoner for lenvatinib. We searched the PubMed database for full-text articles on lenvatinib published in the last 10 years using the search terms “lenvatinib,” “hepatocellular carcinoma,” renal cell carcinoma,” “thyroid carcinoma,” “and “endometrial carcinoma”. A total of 1053 studies were identified, of which 60 were included in this review.

Best medicine practice is thought to be based on evidence. Inferential statistics allow us to establish the strength of evidence in favor of or against a new research finding. The P value has been considered a reliable universal marker indicative of statistical significance of a study, thus driving the majority of practice-changing developments. Of late, the reign of the P value has been increasingly challenged by failure of replication of results in successive studies necessitating withdrawals of drug approvals. For the purpose of this narrative review, we performed a detailed literature search to identify relevant articles from the PubMed database and Cochrane library. We aimed to evaluate the drawbacks of the utilization of P value in a dichotomous way around a fixed cut-off of 0.05. Our review suggests that the P value must be interpreted as a continuum with smaller values depicting greater significance. The possible substitutes for P value are also discussed to enable a rational interpretation of results of new discoveries.