HCG Cancer Hospital

Human papillomavirus (HPV)-related oropharyngeal squamous cell carcinomas (OPSCC) represent a distinct subgroup of head and neck squamous cell carcinoma (HNSCC) characterized by better prognosis and increased radiosensitivity compared to HPV-negative OPSCC. However, current diagnostic and monitoring methods, including tissue biopsies and imaging, are insufficient for precise risk stratification and early detection of recurrence, leading to challenges in treatment de-escalation and surveillance strategies. Circulating tumor HPV DNA (ctHPV-DNA) has emerged as a promising minimally invasive biomarker that offers tumor-specific detection and monitoring capabilities, potentially transforming the management of HPV-related OPSCC through early disease detection, treatment response assessment, recurrence surveillance stratification, and disease monitoring. Despite encouraging results from early clinical studies, current use is limited to trial settings. Large-scale prospective studies are needed to validate its clinical utility and determine whether early ctHPV-DNA testing can improve patient outcome while reducing treatment related morbidity. This review outlines the biological rationale, technological approaches, and current clinical evidence for ctHPV-DNA in HPV-related OPSCC, emphasizing its potential role in treatment monitoring and surveillance.

ABSTRACT Hypopharyngeal cancer usually presents at the locally advanced stage and is relatively uncommon. Early diagnosis is difficult because of recesses and spaces around the larynx, which delay presentation until local progression or neck metastasis occurs. Almost all patients are treated with curative intent. As surgical approaches are functionally and cosmetically morbid, nonsurgical modalities are preferred. This review emphasizes a comprehensive diagnosis workflow, the integration of less toxic induction chemotherapy regimens, and a multidisciplinary approach to patient care. It aims to optimize treatment outcomes, while preserving quality of life, particularly in the Indian healthcare context.

Multiple myeloma (MM) exhibits significant genetic heterogeneity with mutations in the MAPK pathway being increasingly recognized as drivers of progression and treatment resistance. This study is the first to employ droplet digital PCR (DD-PCR) on bone marrow formalin-fixed paraffin-embedded (BM-FFPE) tissue to quantify BRAF V600E and NRAS Q61R mutations in MM, and the first such investigation conducted in an Indian MM cohort. Mutations were identified in > 80% of samples. BRAF V600E displayed stage-specific variation, being lowest in intermediate MM and significantly higher in advanced disease (MMII vs MMIII, p = 0.0453). Burden declined after treatment (p = 0.038) and correlated with stage (β = -36.95, p = 0.0041) and lytic lesions (β = -25.97, p = 0.0268). NRAS Q61R was enriched in progressive disease (p = 0.02) and showed an upward trend with advancing stage (β = 14.38, p = 0.0686). Higher BRAF and NRAS burdens were associated with reduced 2-year progression-free survival (PFS). We show that DD-PCR appliedto BM-FFPE samples is both feasible and informative. However, our study has inherent limitations: DD-PCR measurements can be influenced by sampling biases, droplet variability and FFPE DNA quality. Our single-centre design and small cohort size limit generalizability but demonstrate the potential for DD-PCR to complement sequencing and clinical stratification if validated in larger populations.

ABSTRACT Background: Due to the complex histological and genomic nature of sarcomas, diagnosing and treating them has proven challenging. Delving into the genomic profiles and molecular markers linked to different sarcoma subtypes will aid in overcoming these obstacles and identifying new potential therapeutic targets. Objectives: The primary objective of this study was to investigate the genomic complexity of sarcoma, while the secondary objective was to identify potential therapeutic targets in the patients with sarcoma from India. Materials and Methods: This retrospective observational study was conducted from January 2020 to February 2024 at 4basecare Precision Health Pvt. Ltd., Bengaluru, India. We carried out comprehensive genomic profiling using gene panels or exome sequencing, including assessment of immunotherapy biomarkers (tumor mutation burden (TMB), microsatellite instability (MSI), programmed death-Ligand 1 (PD-L1)), in a cohort of 263 patients with sarcoma, categorized into 25 sarcoma types, for the present retrospective analysis. Results: We included 263 patients with sarcoma in our study and identified a diverse landscape of pathogenic variants across 138 genes, in 69.5% (183 patients) of the cohort. SNVs were prevalent in TP53 (25.1%; 66 patients), KIT (5.7%; 15 patients), PTEN (4.6%; 12 patients), and RB1 (4.6%; 12 patients), while CDK4 (5.2%; 17 patients) and MDM2 (5.7%; 15 patients) gene amplifications and SS18-SSX2 (1.1%; 3 patients), EWSR1-FLI1 (0.8%; 2 patients), and ASPSCR1-TFE3 (0.8%; 2 patients) gene fusions were recurrent. The majority of the patients harbored mutations affecting cell cycle control (39.2%; 103 patients), PI3K/AKT/MTOR (17.9%; 47 patients), and RAS/RAF/MAPK (14.8%; 39 patients) pathways. The average TMB was 7 mutations/mb, with 13.3% (35 patients) classified as TMB-H. Around 59.3% of the cohort (156 patients) harbored clinically actionable variants of therapeutic significance, including 8.7% of the cohort (23 patients) who were eligible for FDA/NCCN approved therapies. Conclusion: The findings emphasize the clinical usefulness of genomic profiling in guiding precision medicine for sarcoma treatment. Our research offers valuable insights into the genetic makeup of sarcomas, serving as a basis for devising efficient and precise diagnostic approaches and for planning preclinical and clinical studies to develop innovative treatment strategies.

ABSTRACTIntroductionThe DMAIC approach is a five‐phase improvement cycle which enables the advancement of pre‐existing processes and was implemented as part of the “lean” process improvement initiative. The present study aims to improve the work efficiency of chemotherapy daycare unit (CDU) at a cancer hospital. The objectives include studying the process flow of the CDU, estimating the patient wait time (PWT) before infusion at the CDU, and implementing new measures to improve its functioning.MethodsIn this quasi‐experimental study, PWT of the CDU process was assessed and its work efficiency was analyzed using other parameters of functioning. The research team implemented a planning system using “lean” methods for reducing the patient contact points in the hospital, streamlining the workflow of patient services at CDU and reducing the laboratory waiting time. The patient satisfaction survey enabled measuring the quality of care at CDU.ResultsThe study methodology was “lean‐DMAIC,” which enabled an improvement in the activities performed by the CDU staff. The mean difference in PWT between the two groups (pre‐ and postintervention) was 13.93 min, which is a significant (p < 0.001) reduction (19%) in the mean PWT values. Although the patient satisfaction survey did not show significant results for the general questionnaire conducted on study subjects (95 patients each in the pre‐ and postintervention groups), the intervention‐specific questionnaire on the cohort of 20 patients showed a significant mean difference (µ = 4.2 ± 0.3 and 4.8 ± 0.2, p < 0.001) between the pre‐ and postintervention groups.ConclusionThe results of the study implicate the potential of revising the process flow for a subset of oncology patients, and its impact on the efficiency of CDU. Adopting a lean technique in the study resulted in an improvised work approach and an anticipative growth in revenue generation.

To optimize NTO parameters in non-coplanar RapidArc (RA) stereotactic radiosurgery (SRS) for multiple brain metastases and compare them with HyperArc (HA) plans. Thirty patients with multiple brain metastases, receiving 21Gy prescriptions, were retrospectively enrolled, with lesions ranging from two to eight and volumes between 0.27 and 10.56 cm3. Non-coplanar RapidArc plans utilized manual NTO (RA-mNTO) with varying dose fall-off values (0.1mm-1, 0.5mm-1, 1.0mm-1, 2.0mm-1, 3.0mm-1) and end doses (50%, 25% & 10%). Additionally, two HyperArc plans were generated: HA-ALDO used Automatic Lower Dose Objectives with SRS NTO, while HA-mNTO used the same beam geometry with manual NTO parameters optimized from RA-mNTO plans. TrueBeam with High-Definition Multi-leaf Collimators (HDMLC), 6 MV Flattening Filter Free (FFF) Beam at a maximum dose rate of 1400 MU/min, and Eclipse version 16.1 TPS were used. Plans were assessed for Paddick Conformity Index (CI), Gradient Index (GI), Homogeneity Index (HI), normal brain doses (V18Gy, V15Gy, and V12Gy), Monitor Units (MUs), and delivery accuracy using aS1200 Digital Megavolt Imager (DMI) with 2%/2mm gamma criteria. Statistical analysis utilized integrated scoring and the Wilcoxon signed-rank test. RA-mNTO plans with 0.5mm⁻1 dose fall-off and 10% end-dose showed superior dosimetric outcomes: CI (0.85 ± 0.08), GI (3.63 ± 0.87), and HI (0.36 ± 0.06) compared to HA-ALDO (CI 0.84 ± 0.09, GI: 3.97 ± 0.85, HI: 0.39 ± 0.07) and HA-mNTO (CI 0.83 ± 0.08, GI: 3.60 ± 0.93, HI: 0.40 ± 0.06). MUs were comparable: RA-mNTO (9679 ± 1882), HA-ALDO (9509 ± 1315), and higher for HA-mNTO (10,457 ± 1980). RA-mNTO plans exhibited significantly lower normal brain doses (V18Gy: 1.78 ± 1.23, V15Gy: 3.54 ± 2.37, V12Gy: 6.21 ± 4.09) compared to HA-ALDO (V18Gy: 2.02 ± 1.34, V15Gy: 4.09 ± 2.66, V12Gy: 7.15 ± 4.56) and HA-mNTO (V18Gy: 1.85 ± 1.20, V15Gy: 3.68 ± 2.33, V12Gy: 6.36 ± 3.97). All techniques achieved > 98% gamma pass rate. Non-coplanar RA plans with optimized mNTO settings outperformed HyperArc plans in all studied dosimetric parameters for SRS treatment of multiple brain metastases.