Purpose:Consensus guidelines from IBS-GEC ESTRO-ABS (Indian Brachytherapy Society- Groupe Européen de Curiethérapie - European Society for Radiotherapy and Oncology- American Brachytherapy Society) for computed tomography (CT)-based contouring have recently introduced possibilities of CT-based adaptive brachytherapy (BT) for cervical cancer. The present study attempts to validate the guidelines by using magnetic resonance imaging (MRI) at diagnosis and in a pre-BT environment. Methods and Materials:The study involved patients with stages IIB to IVA carcinoma of the cervix who had pretreatment MRI and were treated with definitive chemoradiation and hybrid-interstitial BT from April 1, 2022, to October 1, 2023. The target volumes-high-risk clinical target volume (HRCTV), intermediate-risk clinical target volume (IRCTV), and organs-at-risk that included bladder, rectum, and sigmoid-were prospectively delineated on BT planning CT using BT planning MRI for guidance, as per IBS-GEC ESTRO-ABS recommendations by a radiation oncologist. The dimensions, volumes, doses, and Dice similarity coefficient on CT were compared with those on MRI images. Results:Two hundred eight scans from 104 sets of 52 patients of CT and magnetic resonance scans were the basis for this study. With respect to dimensions, CT overestimated HRCTV maximum width, IRCTV width at point A, and maximum thickness of HRCTV and IRCTV compared with MRI (P values, <.001, <.001, .049, and .007, respectively). In analysis of organs-at-risk volumes, CT overestimated sigmoid and rectum volumes, with median difference of paired values of 7.2 (Interquartile range [IQR], 3.1-13.6) and 7.8 (IQR, 3.6-12.8) and P values of <.001 and .003, respectively. Bladder 2cc and sigmoid 2cc doses were underestimated with CT images, with median difference of paired values of 0.5 (IQR, 0.3-0.9) and 0.5 (IQR, 0.3-0.8) and P values of <.001 and .003, respectively. There was an insignificant difference in HRCTV and IRCTV doses between CT and MR images. The median Dice similarity coefficients of HRCTV, IRCTV, bladder, rectum, and sigmoid were 0.72, 0.78, 0.76, 0.68, and 0.46, respectively. Conclusions:Despite the dimensional differences, there was no dosimetric difference in HRCTV and IRCTV. CT-based contouring using IBS-GEC ESTRO-ABS recommendations, with MRI at diagnosis and BT, similar to the MRI at diagnosis + pre-BT MRI + CT at brachytherapy environment, is safe, convenient, and addresses logistic issues in institutions, especially in low- and middle-income countries.

Purpose:Brachytherapy remains integral component in curative-intent management of locally advanced cervical cancer, with overall treatment time (OTT) strongly influencing outcomes. In this study, we intended to analyze single-application two-fraction (SATF) high-dose-rate (HDR) brachytherapy feasibility, treatment outcomes, and toxicities. Material and methods:This study included 238 patients with stage IB-IVA (FIGO 2018) cervical cancer treated with definitive external beam chemoradiation 45 Gray (Gy) in 25 fractions and concurrent weekly cisplatin, followed by SATF HDR brachytherapy (7 Gy × 4 fractions in two applications, ≥ 12 hours apart) between April 2020 and December 2022. Primary endpoint was 3-year disease-free survival (DFS), while secondary endpoints were 3-year overall survival (OS), local control (LC), and acute/late toxicities (as per RTOG criteria). Results:Out of 238 treated patients, majority of them had squamous cell carcinoma (96.6%) and locally advanced disease (stage IIB: 47.5%, IIIC1r: 28.2%). Intracavitary brachytherapy was used in 89.5% of cases. The mean EQD2 D90 HR-CTV and point A were 88 Gy and 77.7 Gy, respectively. The mean EQD2 of the bladder 2 cc, rectum 2 cc, and sigmoid 2 cc were 85.1 Gy, 66.0 Gy, and 69.9 Gy, respectively. At a median follow-up of 45 months, 73 DFS events and 69 deaths were recorded. The 3-year DFS and OS were 70.2 ±3% and 72.2 ±3%, respectively. On univariate analysis, stage IIB was associated with a significantly lower hazard of recurrence (HR: 0.27, 95% CI: 0.11-0.65, p = 0.003) and death (HR: 0.23, 95% CI: 0.10-0.57, p = 0.001). No acute grade ≥ 3 toxicities were reported. At 24 months, the cumulative actuarial rates for late grade ≥ 2 late gastrointestinal (GI) and genitourinary (GU) toxicities were 12.2% and 1.7%, respectively, with grade ≥ 3 GI toxicity (8.2% at 12 months) showing a declining trend over time. Conclusions:SATF HDR brachytherapy with chemoradiation offers favorable disease control and acceptable late toxicities, with good dosimetry while optimizing OTT in cervical cancer management. This approach is feasible and especially effective in high-volume, resource-constrained LMIC settings.

PURPOSE The human microbiome is increasingly recognized as a key modifier of carcinogenesis, immune regulation, and treatment response. In lung cancer, characterization of both respiratory and gut microbiomes offers opportunities to identify biomarkers and therapeutic targets. However, methodologic variability limits reproducibility and clinical translation. The objective was to systematically evaluate current microbiome testing methodologies in lung cancer, focusing on sequencing-based profiling and short-chain fatty acid (SCFA) analysis. METHODS A systematic search of PubMed, Scopus, and Web of Science identified human lung cancer studies (2014-2023) employing 16S rRNA gene sequencing, shotgun metagenomics, metatranscriptomics, or SCFA quantification. Eligible studies were assessed per PRISMA guidelines for design, analytic workflow, and key findings. RESULTS Eighty-seven studies met inclusion criteria. Most (86%) used 16S rRNA sequencing, primarily on bronchoalveolar lavage, bronchial brushings, or stool. Shotgun metagenomics (9%) provided higher taxonomic and functional resolution, while SCFA analysis (14%), mainly via gas chromatography-mass spectrometry or liquid chromatography-mass spectrometry, explored gut-lung interactions. Substantial heterogeneity was noted in DNA extraction, targeted 16S regions, sequencing platforms, and bioinformatic pipelines, complicating cross-study comparison. Across studies, lung cancer samples showed reduced alpha diversity and enrichment of taxa such as Streptococcus and Veillonella . SCFA studies suggested higher fecal butyrate and propionate levels were associated with favorable immunotherapy responses. CONCLUSION Methodologic inconsistency across microbiome testing platforms remains a major barrier to validation of microbial biomarkers in lung cancer. Standardized protocols for sampling, sequencing, and SCFA quantification are essential for reproducibility. Incorporating harmonized microbiome assays into immuno-oncology trials could improve biomarker reliability, refine patient stratification, and advance precision cancer care.

Purpose Consensus guidelines from IBS-GEC ESTRO-ABS for CT-based contouring has recently introduced possibilities of CT-based adaptive brachytherapy (BT) for cancer cervix. The present study attempts to validate the guidelines by using MRI at diagnosis and in pre-BT environment. Methods and Materials The study involved Stage IIB to IVA patients of carcinoma cervix with pre-treatment MRI, treated with definitive chemoradiation and hybrid-interstitial BT, during 01 April, 2022 to 01 October, 2023. The target volumes HRCTV, IRCTV and OARs that included bladder, rectum and sigmoid were prospectively delineated on BT planning CT using BT planning MRI for guidance, as per IBS-GEC ESTRO-ABS recommendations by a radiation oncologist. The dimensions, volumes, doses, DSC on CT were compared with that of MRI images. Results Two hundred eight scans from 104 sets of 52 patients of CT and MR scans, were basis for this study. With respect to dimensions, CT overestimated HRCTV maximum width, IRCTV width at Point A and maximum thickness of HRCTV and IRCTV, compared to MRI p-value: <0.001, <0.001, 0.049, and 0.007, respectively. In analysis of OAR volumes, CT overestimated sigmoid and rectum volumes with median difference of paired values: 7.2(IQR3.1-13.6), and 7.8(IQR3.6-12.8), p-value: <0.001 and 0.003, respectively. Bladder2cc and Sigmoid2cc doses were underestimated with CT images with median difference of paired values: 0.5(IQR0.3-0.9) and 0.5(IQR0.3-0.8), p-value: <0.001 and 0.003, respectively. There was insignificant difference in HRCTV and IRCTV doses between CT and MR images. The median DSC of HRCTV, IRCTV, Bladder, Rectum and Sigmoid were 0.72, 0.78, 0.76, 0.68 and 0.46, respectively. Conclusion Despite the dimentional differences there was no dosimetric difference in HRCTV and IRCTV. CT based contouring using IBS-GEC ESTRO-ABS recommendations with MRI at diagnosis and brachytherapy, similar to the MRDG-Pre BT MR/CTBT environment, is safe, convenient and addresses logistic issues in institutions, especially in low middle-income countries (LMICs).

Objectives: Trastuzumab deruxtecan (T-DXd) has demonstrated significant efficacy in human epidermal growth factor Receptor 2 (HER2)-positive metastatic breast cancer (mBC). However, real-world data, particularly from diverse populations like India, are limited. This study aimed to assess the real-world safety and efficacy of T-DXd in Indian patients with HER2-positive mBC. Material and Methods: This retrospective, single-centre study analysed medical records of 24 patients with HER2-positive mBC treated with T-DXd at a tertiary care centre in India. Patients received T-DXd 5.4 mg/kg every 3 weeks. Data collected included demographics, disease characteristics, treatment details, response rates (per RECIST 1.1), progression-free survival (PFS), and adverse events (AEs). Results: The median patient age was 50 years (range 36–71). The majority (86.9%) were still on treatment at data cutoff (median follow-up 6 months). The overall response rate (ORR) was 66.7% (complete response CR 4.2%, partial response PR 62.5%), with a disease control rate (DCR) of 87.5%. The median PFS was not reached, with an estimated 1-year PFS of 72.7% ± 12.5%. The most common AEs were nausea (45.8%), fatigue (33%), neutropenia (25%), and vomiting (20.8%). Interstitial lung disease (ILD) occurred in 3 patients (12.5%). The observed PFS was similar for patients treated with T-DXd in 2nd/3rd versus 4th+ lines. Conclusion: This real-world study demonstrates the efficacy and manageable safety profile of T-DXd in Indian patients with HER2-positive mBC, even in heavily pretreated patients and those receiving treatment in later lines, supporting its continued use in this population. The findings largely align with clinical trial data.

BACKGROUND:Locally advanced pancreatic cancer (LAPC) is currently treated with chemotherapy (CT) alone or CT combined with radiation therapy (RT) (CT+RT). There is no robust evidence supporting one over the other. The present study compares the two treatment modalities in terms of their survival outcomes and safety profile. METHODS:The retrospective study includes 29 nonmetastatic, unresectable, LAPC patients who were treated with CT+RT (21 patients) or CT alone (8 patients) during November 2019 to September 2023. CT consisted of FOLFIRINOX or Gemcitabine-based regimens. CT+RT patients were treated with conventional (50.4 Gy/28fr) as well as hypofractionated RT dose schedules (39 Gy/13fr, 25 Gy/5fr, and 42 Gy/6fr). The primary endpoint of the study was the median overall survival (OS), and the secondary endpoints were the median progression-free survival (PFS) and acute and late radiation-induced toxicities. RESULTS:At a median follow-up of 24 months, patients of CT+RT group had prolonged survival compared to patients of CT alone group with median OS of 20 months versus 7 months (P = 0.0032) and median PFS of 15 months versus 5 months (P = 0.029). The majority of toxicities in CT+RT group were Grade 1-2 around 79%. However, Grade 3 or more late event was seen only in 1 (5%) patient. CONCLUSION:Incorporating radiation therapy along with CT should be the standard approach for unresectable LAPC patients improving survival with acceptable toxicities.

HER2-positive metastatic breast cancer (MBC) represents a challenging subtype of breast cancer, characterized by aggressive disease and poor clinical outcomes. Trastuzumab emtansine (TDM1), an antibody-drug conjugate combining trastuzumab and emtansine, has demonstrated efficacy in clinical trials as a second-line treatment for patients progressing after prior therapies. This study aims to provide real-world evidence on the efficacy and safety of TDM1 in HER2-positive MBC patients. A retrospective analysis was conducted on 70 HER2-positive MBC patients treated with TDM1 at our centre between January 2020 and December 2022. Clinical characteristics, progression-free survival (PFS), overall survival (OS), response rates, and toxicity were evaluated using hospital records. PFS and OS were calculated using Kaplan-Meier methods, and survival curves were compared with log-rank tests. The median age of patients was 47 years, with a majority presenting with advanced disease and prior treatment lines. The median PFS was 6.1 months (95% CI, 4.5-7.6), and the median OS was 14.4 months (95% CI, 10.2-18.0). The objective response rate was 75.7%, with 12.8% achieving a complete response and 62.8% a partial response. PFS was significantly longer in hormone receptor-positive patients compared to hormone receptor-negative patients (8.1 vs. 4.1 months, p = 0.035). Toxicity was manageable, with grade 3-4 adverse events including elevated transaminases (8.5%), thrombocytopenia (5.7%), and anemia (4.2%). The efficacy of TDM1 in this real-world cohort aligns with clinical trial data, though PFS and OS were somewhat lower compared to trials, likely due to the inclusion of patients with more extensive disease and prior treatments. Notably, TDM1 demonstrated activity against CNS metastases and a manageable safety profile, with higher incidence of hepatic and hematologic toxicities. Our study supports the use of TDM1 as a viable option for treating HER2-positive MBC in routine clinical practice, confirming its effectiveness and safety profile observed in clinical trials.

Metaplastic breast cancer with heterologous mesenchymal differentiation, known earlier as carcinosarcoma, consists of both infiltrating ductal carcinoma cells and mesenchymal cells, and is associated with an aggressive course. The mesenchymal component is rarely endothelial, with only two previously reported cases. The present case is the third among those. Moreover, the disease outcome was good, unlike the usual course of carcinosarcoma. A 59-year-old multiparous woman of Indo-aryan ethnicity developed a lump in her left breast and was diagnosed with breast carcinosarcoma having an endothelial component, with the help of histopathological examination and immunohistochemistry. The tumor was surgically removed; then the patient received adjuvant chemotherapy, epirubicin, and cyclophosphamide, followed by adjuvant radiotherapy to the whole breast, followed by tumor bed boost. The patient was clinic-radiologically disease-free even at 26 months post-treatment. Surgery followed by adjuvant chemotherapy and radiotherapy gives better outcomes compared with surgery alone, with a doubtful role of neoadjuvant chemotherapy. Targeted therapies can be considered in patients not responding to conventional treatment.

Chronic diarrhea and abdominal pain after radiotherapy continue to be a problem in cancer survivors. Gut microbiomes are essential for preventing intestinal inflammation, maintaining intestinal integrity, maintaining enterohepatic circulation, regulating bile acid metabolism, and absorption of nutrients, including fat-soluble vitamins. Gut microbiome dysbiosis is expected to cause inflammation, bile acid malabsorption, malnutrition, and associated symptoms. Postradiotherapy, Firmicutes and Bacteroidetes phylum are significantly decreased while Fusobacteria and other unclassified bacteria are increased. Available evidence suggests harmful bacteria Veillonella, Erysipelotrichaceae, and Ruminococcus are sensitive to Metronidazole or Ciprofloxacin. Beneficial bacteria lactobacillus and Bifidobacterium are relatively resistant to metronidazole. We hypothesize and provide an evidence-based review that short-course targeted antibiotics followed by specific probiotics may lead to alleviation of radiation enteritis.

IntroductionThe revision of International Federation of Gynaecology and Obstetrics staging in 2018 with recommendations to include cross-sectional imaging and a separate stage for node positive disease have opened a lot of uncertainties in implementing the correct treatment approach in these patients. While studies have suggested higher chances of occult para-aortic lymph node (PALN) even with advanced imaging, especially in pelvic node positive disease which tend to recur after pelvic radiation therapy. This study intends to study these patients and isolate the subset who will benefit most from elective PALN irradiation.Methods and analysisThis is an ongoing multicentric phase III randomised controlled trial with a sample size of 274 subjects in two arms (137 in each arm) to determine the superiority of limited elective para-aortic irradiation compared with no irradiation. Arm one includes radiation to the lower PALN and pelvis; Arm two includes radiation to the pelvis. Concurrent chemotherapy followed by brachytherapy is standard in both arms. Patients with cervical cancer and radiologically positive pelvic LNs aged>18 years and<70 years are screened for the study. The primary endpoint of this study is 3-year disease-free survival. The secondary endpoints include 3-year para-aortic recurrence-free survival, 3-year distant metastasis-free survival, 3-year overall survival, acute and late toxicity, quality of life. Translational study to evaluate systemic immune response by FAPI-PETCT (fibroblast activator protein inhibitor positron emission tomography) and assessment of p16, L1 cell adhesion molecule (L1CAM) and protein death ligand-1 (PDL-1) expression by immunohistochemistry.Ethics and disseminationThe study has been approved by the institutional ethics committee and will be routinely monitored according to standard guidelines. The results of the study will be published in peer-reviewed scientific journals, presented at conferences and submitted to regulatory authorities.Trial registration numberThe study was registered on 17 January 2022 under CTRI/2022/01/039495 (http://ctri.nic.in).

Purpose: For cervical cancer patients, intra-cavitary brachytherapy (ICBT) is utilized with various dose-rate systems, such as low-dose-rate (LDR), high-dose-rate (HDR), and pulsed-dose-rate (PDR). This retrospective analysis aimed to compare the therapeutic outcomes of cervical cancer patients treated with either LDR-, HDR-, or PDR-ICBT. Material and methods: A total of 613 patients were treated with pelvic external beam radiation therapy (EBRT), followed by either LDR- (271 patients), HDR- (259 patients), or PDR- (83 patients) ICBT. Point-based planning was performed according to orthogonal radiographs in LDR patients, and computed tomography (CT) imaging in HDR and PDR patients. ICBT prescribed dose was as follows: for LDR treatment, 30 Gy in a single-session; for HDR: 7 Gy x 3 fractions (once a week fraction); and for PDR: 27 Gy in an hourly pulse of 70 cGy, with all the doses prescribed at point A. Radioactive source used was cesium-137 for LDR, and iridium-192 for HDR and PDR treatments. Results: Loco-regional control (LRC) rate was 74%, 75%, and 77% in LDR, HDR, and PDR groups, respectively (p p = 0.80). The 5-year overall survival (OS) in the three groups, i.e., LDR, HDR, and PDR was 63%, 64%, and 68%, respectively (p p = 0.77). Severe late toxicity (RTOG grade >= 3) rate in the three groups was comparable (LDR, 12%; HDR, 8%; and PDR, 8.9%, p = 0.36). Conclusions: Our study revealed comparable LRC, 5-year OS, and late toxicity rates using three dose-rate systems. Lower OS rates were observed in LDR group for stage III patients compared with patients in HDR and PDR groups. Therefore, we suggest that LDR should be used with caution while treating stage III patients.

OBJECTIVES:With sensitive imaging for breast cancer, the question arises whether present-day oncologists treat dOMBC with palliative systemic therapy (ST), which, a few years earlier, would have been treated with curative intent. We retrospectively analyzed outcomes of dOMBC treated with curative intent using a combination of surgery, metastasis-directed radiotherapy (RT), and adjuvant/neoadjuvant ST and have also explored the possible role of total lesional glycolysis of metastases and p53 immunohistochemistry in predicting outcomes. METHODS:Data were collected from a prospectively maintained database using electronic medical records and Radiation Oncology Information System. In the study, dOMBC was defined as up to 3 metastatic sites, all amenable to treatment with ablative RT and primary and axillary disease amenable to curative surgery. Patients were treated with surgery, ST, and RT. RESULTS:Patients underwent either breast conservation surgery or modified radical mastectomy. Patients were treated with 6 to 8 cycles of chemotherapy in the neoadjuvant and/or adjuvant setting. Hormone receptor-positive patients received either tamoxifen or aromatase inhibitors. Trastuzumab was offered to Her-2-neu receptor-positive patients. RT included locoregional RT and metastases-directed ablative body RT. The median progression-free survival was 39 months (95% CI: -28.7 to 50.1 mo). Two and 3 year estimated disease-free survival (DFS) was 79% and 60.5%, respectively. The median overall survival was not reached. The estimated 3-year overall survival was 87.3%. Total lesional glycolysis of metastases score and p53 status did not affect DFS. CONCLUSION:Combination treatment of surgery, metastases-directed ablative RT, and ST may provide prolonged DFS in dOMBC.

The treatment landscape for localized and regional prostate cancer includes active surveillance, radiation therapy (RT), and radical prostatectomy (RP). Population-based studies comparing RP to radiation reveal conflicting results due to methodological flaws. This systematic review and pooled analysis of studies aim to compare cause-specific survival (CSS), overall survival (OS), disease-free survival (DFS) and toxicity outcomes, comparing RP to RT in the management of prostate cancer. This systematic review search included the PubMed, Embase, and Cochrane libraries according to the PRISMA statement with the inception of each database up to June 24, 2023. Randomized phase 2 or 3 clinical trials that compared RP to RT in prostate cancer were included. The forest plot for the Odds ratio (OR) was plotted using the Mantel-Haenszel method, and the Z test was used to assess significance. A fixed effects model was used for meta-analysis. The search yielded seven completed randomized clinical trials and four ongoing trials. The majority of complete trials had low to intermediate-risk patient populations. OR for OS was 1.00 with 95% CI, 0.71-1.41 (P-value: 0.98), CSS OR was 0.99 with 95% CI, 0.45-2.18 (P-value 0.11), OR for DFS was 1.26 with 95% CI, 0.89-1.78 (P-value 0.19) when comparing RP to RT. The rate of distant metastatic disease was 2.3% in the RP versus 2.9% in the RT at 10 years. The rate of second malignant neoplasms was 4.5% in the RP compared to 4.2% in the RT arm at 10 years. RP caused more urinary symptoms, with a predominance of the need for urinary pads and a higher incidence of sexual dysfunction, and RT caused a higher incidence of bowel symptoms, such as blood in stools and fecal incontinence. This study provides evidence that the treatment-related outcomes are similar in patients with low to intermediate-risk prostate cancer when comparing RP to RT. Multidisciplinary treatment approaches and factoring patients' values and preferences should form the cornerstone of the ideal treatment option for each patient with localized prostate cancer. Patients with prostate cancer have an equal chance of being cancer-free and alive at 10 years with either RP or RT. In terms of side effects, RP causes more urine leakage and loss of erections, whereas RT tends to cause more bowel side effects, such as blood in stools and fecal leakage.