Venkata Pradeep Babu Koyyala

Head and neck squamous cell carcinoma (HNSCC) remains a major cause of cancer death, and despite advances in surgery, radiation, and chemotherapy, five-year survival in locally advanced disease stays below 50%, with most relapses occurring within two years. Immune checkpoint inhibitors and radiotherapy carry a strong preclinical rationale for synergy: radiation drives immunogenic cell death, releases tumor antigens and danger signals, upregulates MHC class I, and can prime systemic anti-tumor immunity, occasionally producing an abscopal effect. The same treatment, however, can be immunosuppressive - elective nodal irradiation, lymphocyte depletion from large radiation fields, regulatory T-cell recruitment, and PD-L1 upregulation all blunt the response. This review examines whether that synergy translates into clinical benefit across three settings. In metastatic or recurrent disease, adding stereotactic body radiotherapy to nivolumab (MSKCC trial) did not improve response or survival, with no meaningful abscopal effect. In unresectable locally advanced disease, two phase III trials adding checkpoint inhibitors to concurrent chemoradiotherapy - JAVELIN Head and Neck 100 (avelumab) and KEYNOTE-412 (pembrolizumab) — failed their primary endpoints, though a PD-L1 CPS ≥20 subgroup appeared to benefit; in cisplatinineligible patients, PembroRad showed pembrolizumab and cetuximab had comparable efficacy with less toxicity from the checkpoint inhibitor. In the postoperative setting, both KEYNOTE-689 (perioperative pembrolizumab) and NIVOPOSTOP (adjuvant nivolumab) significantly improved survival outcomes in high-risk resected patients. The benefit of combining immunotherapy with radiotherapy in HNSCC therefore lies with postoperative chemoradiation patients, not those treated with concurrent chemoradiation for unresectable disease — and progress in unresectable disease will likely depend on biomarker-driven selection and smarter sequencing rather than layering more drugs onto existing chemoradiation.

Colorectal cancer (CRC) is a heterogeneous disease morphologically, histologically, and molecularly. Most of the studies are on this molecular heterogeneity and their clinicopathological correlation from the western world. Very few studies have been done in India. The aims of this study were to evaluate the clinical and pathological profile of CRCs, to determine the frequency of molecular subtypes of CRCs, to correlate between the molecular subtypes and their clinicopathological features, and to determine the association between different molecular subtypes of CRC. A prospective noninvasive interventional study was done on 50 patients (both outpatients and inpatients) with newly diagnosed CRCs presenting to the Rajiv Gandhi Cancer Institute and Research Centre, Rohini, Delhi, from February 2019 to March 2020. Clinical and histopathological data were collected from case sheets as per the study proforma: history and physical examination, noninvasive and invasive imaging, and histopathological reports. Patients in whom tissue was insufficient or not available for testing for at least three of five molecular markers (KRAS, NRAS, BRAF, MSI, and MLH1 methylation) were excluded. The results were analyzed with SSPS 23.0 software. For comparison of the frequencies among groups, the chi-squared test and the Fisher exact test were used. A p-value of less than 0.05 was considered statistically significant. The median age was 53 years. The majority of the males (54%) had CRC and 44% were right-sided colon tumors. Of the 50 patients with CRC, 40, 0, 4, and 4% had KRAS mutation, NRAS and BRAF mutation, and deficient mismatch repair (dMMR), respectively. KRAS mutation was significantly associated with upfront liver metastases (p = 0.02) and well/moderate differentiation (p = 0.02). BRAF wild-type tumors were likely to be well differentiated (p = 0.02), and moreover, half of them (52%) had MLH1 promoter methylation. The proportion of dMMR was higher in male patients (p = 0.04). Deficient mismatch repair was associated with well/moderate differentiation (p = 0.02), early stage (p =0.02), and mild peritumoral lymphocytes (p = 0.01). None of the dMMR patients had stage IV CRC. In all, 27% of the patients (3/11) with dMMR tumors had germline mutation of the dMMR genes. The majority of dMMR tumors (43%, 3 out of 7) had MLH1 promoter methylation. Overall, 45% (5/11) of dMMR tumors harbored KRAS mutation. In conclusion, this is a prospective study evaluating the correlations between RAS/BRAF mutation and dMMR status with clinicopathological characteristics in Indian CRC patients, which is slightly similar to worldwide reports with some exceptions. To the best of our knowledge, this is the first study to evaluate the molecular marker combinations in CRC in India.

Inflammatory bowel disease (IBD), encompassing Crohn's disease and ulcerative colitis, significantly increases the risk of colitis-associated cancer (CAC). Chronic inflammation, a key contributor to carcinogenesis, disrupts immune surveillance, induces deoxyribonucleic acid (DNA) damage, and alters genetic and epigenetic pathways. Molecular pathways such as STAT3, mTOR, and NF-κB drive CAC progression, while unique microbiome alterations—loss of Faecalibacterium prausnitzii and increases in Escherichia coli and Fusobacterium species—exacerbate the inflammatory milieu. CAC accounts for 2% of all colon cancers and up to 15% of IBD-related deaths. Risk correlates with IBD duration, increasing approximately 1% annually after the first decade. Surveillance via colonoscopy is crucial, with chromoendoscopy recommended for high-risk cases. Preventive drugs, including aminosalicylates, thiopurines, and biologics, offer modest benefits but lack conclusive evidence. Post-CAC diagnosis, immunosuppressants are discontinued in favor of corticosteroids, with 5-aminosalicylates continued as needed. The use of immune checkpoint inhibitors remains controversial due to exacerbation of colitis. Emerging insights into the gut microbiota's role in IBD and CAC may revolutionize prevention and management strategies. Advances in screening, surveillance, and therapeutic approaches have reduced CAC mortality, underscoring the importance of personalized medicine and ongoing research to address these complex conditions.

Background The widespread use of oxaliplatin plus infusional 5-fluorouracil (5-FU) and folinic acid (FOLFOX) in advanced gastric cancers is mainly based on clinical trials conducted at Western/European countries. The prospective data on efficacy and safety of FOLFOX in advanced gastric cancer is lacking from the developing countries. In this prospective observational study, we evaluated the efficacy and toxicity of mFOLFOX-6 in patients with advanced gastric or gastroesophageal junction (GEJ) adenocarcinomas, as first-line palliative chemotherapy. Methods Patients with previously untreated metastatic adenocarcinoma of stomach/GEJ, received mFOLFOX-6 (2 hours infusion of oxaliplatin [85 mg/m²] and folinic acid [400 mg/m²], followed by fluorouracil 400 mg/m² intravenous push, then a 46-hour continuous infusion of 5-FU [2,400 mg/m²]). Cycles were repeated every 2 weeks. The patients were prospectively followed up for response rates and toxicity. Results Sixty-six patients were included in the study with a median age of 57 years. Sixty-two patients were evaluable for response. The overall response rate was 53%, with a disease control rate (overall response and stable disease) of 81.8%. The median progression-free survival was 6 months (95% confidence interval [CI] 5.2–6.7 months) and the median overall survival was 11.5 months (95% CI 9.0–13.9 months). Ascites at presentation and more than one site of metastasis are associated with significantly lower survival on the log-rank test. Gastrointestinal and hematological toxicities were predominant, with rates of grade 3 to 4 nausea/vomiting (13.6%), anemia (15.1%), and neutropenia (13.6%). Among other toxicities, neurosensory toxicities were common. Four (6%) patients had grade 3 peripheral neuropathy. Conclusion mFOLFOX-6 is an active and well-tolerated chemotherapy regimen in advanced adenocarcinoma of stomach/GEJ. This regimen has similar response rates and treatment outcomes with lesser grade 3 or 4 toxicities than that of triplet regimens compared to historical studies. Received: 14 June 2023 Accepted: 26 June 2024 Article published online: 22 July 2024 © 2024. MedIntel Services Pvt Ltd. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/) Thieme Medical and Scientific Publishers Pvt. Ltd. A-12, 2nd Floor, Sector 2, Noida-201301 UP, India

Pancreatic cancer is an aggressive malignancy. Recurrences are very high despite high-quality surgery necessitating adjuvant therapy. The evolution of adjuvant therapy took several decades and gradually evolved from single-agent chemotherapy to multi-agent chemotherapy. The two important agents that are active in pancreatic cancer are 5-fluorouracil and gemcitabine, and with several combinations showing better results in the subsequent trials, the most recent trial PRODIGE 24 shows a median survival of 54.4 months. The role of neoadjuvant therapy is still evolving in resectable cancers. The role of adjuvant radiotherapy is not well defined due to controversial results from historical trials.

The rising incidence of colorectal cancer (CRC) in India, particularly the prevalence of rectal cancer over colon cancer (0.7:1), has been a growing concern in recent decades; especially notable is the trend of increasing cases among young CRC patients. Given the diverse treatment approaches for rectal cancer globally and the varying economic capacities of patients in low to middle-income countries (LMICs) like India, it is essential to establish consensus guidelines that are specifically tailored to meet the needs of these patients. To achieve this, a panel comprising 30 eminent rectal cancer experts convened to conduct a comprehensive and impartial evaluation of existing practices and recent advancements in the field. Through meticulous scrutiny of published literature and a consensus-building process that involved voting on pertinent questions, the panel formulated management strategies. These recommendations are the result of a rigorous, evidence-based process and encapsulate the collective wisdom and judgment of leading authorities in the field.

After nearly an 8-hour journey, the smile on his newborn face and the first touch were memorable and precious—for any father seeing his first born. The routine of my wife Pavani has changed forever, perhaps for good. And priorities changed in life—both personal and professional. Despite being an anesthetist, she has to bear the pain due to incomplete epidural anesthesia. But, she still managed to smile. The last 9 months changed her levels of endurance permanently to much higher levels. I was engulfed in my oncology fellowship. I just had barely enough time to spend, only a few weekends and evenings with young Viswa. Everything in life seemed absolutely beautiful and exciting. Until one day, Pavani told Viswa does not give eye contact with her and did not have a social smile. I told it's quite normal at that age and asked her not to worry. Her worry persisted as much as my denial that anything was abnormal. As a physician, I was trained to question the diagnosis till I was satisfied with my own findings and able to explain the condition. At last, the father in me overtook the physician in me overtook the father in me to rule out any possible abnormality. Following the first appointment with New Delhi's prime child psychiatrist and a full day's battery of tests, he was labeled as having autistic spectrum disorder. We never knew that these appointments and assessments are going to be a part of our life for years to come. We joined him in a day care, only to see that he never preferred to play with other children. He chose to be around his teacher. He never passed a ball to another child nor did he comprehend what the other child was trying to communicate with him. However, I always wondered how only his mother understands his tantrums and his needs, whether it's his favorite music channel or a fruit. She started supporting mothers of other autistic children who were unable to understand the condition completely and no counseling could be better than a communication between two mothers. One of such event was a phone session with a sister of my colleague whose marriage was disrupted and attempted suicide along with her autistic child, luckily saved in time. The problem of autistic spectrum disorder in India is bigger than it is assumed and less understood than what is needed. I involuntarily became a passive observer of the daily totally new counseling and therapy sessions in action. And I embraced them into my practice. And I am sure that a mother of an autistic child sweeps any new place for safety better than secret services, though looks like exaggeration, one has to witness the act before disagreement! While working at Vizag, I tried to understand and visualize what each of my patients and their families undergo, hearing a diagnosis of cancer. Slowly, most of my patient and family conversations moved beyond cancer and cure. Despite working in a hectic cancer outpatient, from two border states and the districts beyond, for, I never hesitate to spend few extra minutes with every patient and family, trying to make them understand the situation and possible outcomes, so that they can feel better and plan accordingly. Ailments, regardless of whether they are mental or physical, disturb the emotional atmosphere of the family, and a few supportive words during such distressing times matter a lot in restoring some sense of balance and sanity. While Viswa is growing, the problem seems to increase more than him, and I am now equally worried as his mother. Unable to see any improvements over a year at a local therapy center, and, satisfied with the discouraging remarks of a popular adult neurologist, we traveled to Christian Medical College (CMC), Vellore to seek the opinion of their child psychiatry division. Fearing how the rather 900 km overnight journey might impact negatively on Viswa, we planned to cover it by road, in the family car. My decision suddenly provided an answer to a nagging question as to why even poor patients spend a lot of money on motor cabs while cheaper public transport is available. Several cancer patients have poor general condition, some have complications, and some have post therapeutic complications limiting the chance of “normal modes of transport.” I dialed up all my contacts who were ever in CMC and finally uncovered a colleague in the department of child psychiatry. Most psychiatric diagnoses appear to be made by excluding all possible organic causes. It is easier to ride a wild horse than getting a magnetic resonance imaging for a special child. The psychiatrists were kind enough to explain, reassure, and make us understand that the therapy and training were necessary for parents—to be patient with the child to an imperceptible but slow and steady improvement. We were asked to visit pediatric neurologist to exclude anything “organic.” We were astonished by the number of children and their parents waiting at that outpatient department. Even for the pair of us who were doctors, the endless waiting outside consultation chambers, laboratories, and review rooms was physically tiring and mentally exhausting. Relief was in the kind words and courteous language of the very many doctors and the ever-smiling nurses. Insistence on repeating a test at a particular laboratory is often futile. We were warned that reports from laboratory other than their hospital could be erroneous! We were often told that reports from elsewhere for metabolic screens were unreliable! Had it been a seminar or a classroom, the statistician in an oncologist would have been in complete disagreement over such super confident lecture. As I was on the other side of the table, I did not dare to negate his tirade, fearing to see more fatigue in the little eyes of my son. The rigmarole of yet another round of billing, laboratories, and a urine sample from an autistic child could be very daunting! Despite our pleas that Viswa was not toilet trained and...

Background Diffusion-weighted magnetic resonance imaging (DW-MRI) sequences report the cellularity in tissues and 18-fluorodeoxyglucose (18-FDG) positron emission tomography–computed tomography (PET-CT) provides information on glucose metabolism in cells, associated to tumor aggressiveness. The aim of this study was to assess the correlation between quantitative diffusion-weighted magnetic resonance parameters and maximum standardized uptake value (SUVmax) using 18-FDG PET-CT in lung cancer and metastatic lymph nodes. Methods Histologically proven 29 patients of lung cancers were subjected to 18-FDG PET-CT and DW-MRI (parameters: repetition time/time to echo [TR/TE] = 4,000/76 ms; b-values = 0, 400, and 800 s/mm²) between June 2018 and June 2019. SUVmax was calculated on the PET-CT images representing region of interest (ROI) in the tumor. The apparent diffusion coefficient (ADC) values were quantified by placing an ROI over the tumor at a high b-value of 800 mm²/s. Statistical analyses for correlation between SUVmax and ADC were done using Pearson's correlation coefficient (r). Results Significant negative correlation was observed between analyses of ADC and SUVmax for primary lesions of all nonsmall-cell lung cancers (NSCLCs; p < 0.05) and its histological subtype adenocarcinoma (p < 0.05) but not squamous cell carcinomas (p = 0.35). Significant negative correlation was also observed for metastatic lymph nodes of adenocarcinoma (p < 0.05) but not for metastatic lymph nodes of all NSCLCs (p = 0.05) or squamous cell carcinomas (p = 0.55). Conclusions Diffusion-weighted imaging (DWI) with ADC may represent a new prognostic marker due to a significant negative correlation between ADC determined by DWI and SUVmax by PET-CT in NSCLCs. Furthermore, DWI-MRI of the thorax can be added to routine 18-FDG PET-CT for staging and response assessment in lung cancer in prospects. This study was supported by a grant from the Rajiv Gandhi Cancer Institute and Research Centre (RGCIRC) scientific committee for thoracic MRI sequences in 29 patients with lung cancer after an institutional review board (IRB) approval. Article published online: 09 June 2023 © 2023. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/) Thieme Medical and Scientific Publishers Pvt. Ltd. A-12, 2nd Floor, Sector 2, Noida-201301 UP, India

Recently, immunotherapy with anti-PD-1(programmed cell death protein 1) or anti-PD-L1 (programmed cell death ligand 1) antibodies has shown both favorable and durable responses in a subset of patients with metastatic and advanced cancers. Although no robust predictive biomarker for immune checkpoint inhibitors (ICI) has been established till date, PD-L1 immunohistochemistry (IHC) testing has emerged with a passable utility. However, PD-L1 is still far from being a perfect biomarker. Nevertheless, PD-L1 testing by IHC to evaluate the immunoexpression of PD-L1 protein in tumor cells and/or immune cells is a useful predictive biomarker for predicting response to ICI.[1] [2] [3] [4] None Article published online: 28 November 2022 © 2022. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/) Thieme Medical and Scientific Publishers Pvt. Ltd. A-12, 2nd Floor, Sector 2, Noida-201301 UP, India

Hodgkin’s lymphoma (HL) is a curable malignancy that commonly involves the younger population. However, HL can rarely occur in the elderly population (≥60 years) and probably has different biology as compared to the younger counterparts. There was a paucity of data on the clinical and epidemiological profile of the elderly subset with HL in Indian patients who are misdiagnosed and empirically treated as tuberculosis. We have done an analysis of this subset of elderly patients who were registered at our institute. A retrospective chart analysis of HL patients who presented to our center from 2008 to 2016 was conducted. Twenty-eight patients with HL of age ≥60 years were included in this study. Elderly HL comprised 18.67% of the total HL patients registered during this period. The majority were male patients, and the mean age of presentation was 65.9±5.6 years. A Charlson Comorbidity Index (CCI) of ≥2 was seen in 30.77% of the patients. Among these, 84.62% of the patients presented with advanced-stage disease, and 57.69% of the patients presented with B symptoms, which was significantly associated with a high-risk international prognostic score (IPS). Histology-wise, mixed cellularity classical Hodgkin’s lymphoma (MCCHL) and nodular sclerosis classical Hodgkin’s lymphoma (NSCHL) were equally represented (30.76%). Of the patients, 50% had extranodal disease, with the liver being the most frequent site involved. One patient each had bone marrow involvement and bulky disease. CD30, CD15, and CD20 positivity was seen in 84.61%, 50%, and 26.92% of cases, respectively. Among elderly HL patients, males were more commonly represented than females, and patients more often presented with advanced disease and B symptoms and less often with bulky disease and mediastinal mass. Mixed cellularity classical HL is more common in the elderly subset, and significant comorbidities are present in a higher number of elderly HL patients.