Risk-Adapted Target Delineation for Breast Cancer: Controversies and Considerations.

The advent of computed tomography-based planning coupled with modern tools for target delineation and hypofractionated treatment schedules has increased efficiency and throughput for patients with breast cancer. While the benefit of adjuvant radiation therapy (RT) in reducing locoregional recurrences is established, disentangling local versus regional recurrence risks with modern treatment protocols has become an area of active research to de-escalate treatment. Delineation guidelines for nodal regions either attempt to replicate results of conventional RT techniques by translating bony landmarks to clinical target volumes or use landmarks based on the fact that lymphatic channels run along the vasculature. Because direct comparisons of both approaches are implausible, mapping studies of nodal recurrences have reported on the proportion of nodes included in these delineation guidelines, and larger, bony, landmark-based guidelines appear intuitively appealing for patients with unfavorable risk factors. A pooled analysis of these studies is reported here, along with literature supporting the exclusion of the true chest wall from postmastectomy/breast-conserving surgery clinical target volumes and the selective (versus routine) use of bolus during postmastectomy RT. The risk-adapted approach suggested here accounts for the risk of recurrence as well as toxicity and endorses nuanced target volume delineation rather than a one-size-fits-all approach.

Tri-modality therapy in advanced esophageal carcinoma: long-term results and insights from a developing world, institutional cohort.

OBJECTIVE: To evaluate treatment outcomes in patients from a low-middle income country (LMIC) with esophageal carcinoma who underwent esophagectomy after neoadjuvant chemoradiation (NACRT/S). METHODS: Between 2010 and 2020, 254 patients (median follow-up: 53 months) met our inclusion criteria. Out-of-field nodal regions were determined by reviewing individual radiotherapy plans. Cox regression modelling was performed to analyze overall survival (OS) and recurrence-free survival (RFS), while pathological complete response (pCR) prediction utilized Poisson regression. RESULTS: The median OS was 71.4 months (interquartile range: 19.6-∞), RFS did not reach the median and pCR rate was 46%. On multivariable Cox regression, BMI [0.93 (0.89-0.98); 0.94 (0.89-0.99)] and absence of out-of-field node with extranodal extension (ENE)[0.22 (0.09-0.53); 0.30 (0.12-0.75)] influenced OS and RFS, respectively. Age [1.03 (1.01-1.06)], nodal stage [cN2-3 vs cN0: 2.67 (1.08-6.57)] and adventitial involvement [2.54 (1.36-4.72)] also influenced OS, while involved margins [3.12 (1.24-7.81)] influenced RFS. On multivariable Poisson regression, non-CROSS-chemotherapy regimens [0.65 (0.44-0.95)] and residual primary disease on pre-surgical imaging [0.73 (0.57-0.93)] were significantly associated with pCR. The most frequently involved in-field and out-of-field nodal regions were the periesophageal and perigastric (greater and lesser curvature) regions, respectively. CONCLUSION: NACRT/S is feasible and effective in patients from LMIC. Out-of-field ENE merits further investigation as a prognostic factor since it significantly influenced both OS and RFS. ADVANCES IN KNOWLEDGE: The results of clinical trials are replicable in LMICs. Out-of-field ENE is an independent prognostic factor for OS and RFS.

Dosimetric analysis of intensity-modulated radiation therapy and volumetric-modulated arc therapy in comparison with conventional box technique in the treatment of carcinoma cervix: An impact of prosthetic implant.

Introduction: The number of patients for carcinoma cervix with implanted hip prostheses has been increasing worldwide during the past several decades. Technological advancements are useful for delivering higher doses, i.e., dose escalation to the target, but the presence of high-density implanted hip prosthesis creates challenges for the planner. Materials and Methods: A population of 25 patients was selected for the study. Plans were generated using the MONACO treatment planning system keeping the isocenter same. The parameters evaluated for planning target volume (PTV) were D98%, D50%, D2%, Dmax, Dmean, V107%, and V110%. Similarly, the parameters Dmax, Dmean, and D2cc were evaluated for the delineated critical organs. Average monitor units (TMUmean) were also assessed. Results: D98% of PTV was 44.51 (standard deviation [SD]: 0.13) Gy, 44.41 (SD: 0.38) Gy, 44.58 (SD: 0.14) Gy, 44.08 (SD: 0.41) Gy and 44.46 (SD: 0.32) Gy for 4F, intensity-modulated radiation therapy (IMRT), IMRT_WP, volumetric-modulated arc therapy (VMAT), and VMAT_WP techniques, respectively, where WP stands for "without prosthesis". Volume of bowel receiving 45 Gy was 86.82 (SD: 66.38) cm3, 6.97 (SD: 5.77) cm3, 14.11 (SD: 14.29) cm3, 13.31 (SD: 6.57) cm3, and 10.31 (SD: 10.94) cm3 for 4F, IMRT, IMRT_WP, VMAT and VMAT_WP techniques, respectively. Discussion: Radiotherapy is standard care of practice for known cases of cervical malignancies. As per our investigations, VMAT has generated comparable plans in terms of target coverage (D98%) as compared to IMRT and 4F techniques (P = 0.015 and P = 0.002) and with prosthesis also (P = 0.024). The mean dose to the bladder was significantly lesser with IMRT and VMAT. Our results highlight that VMAT has reduced the mean dose to the rectum (P = 0.001) in presence of high-density implant. The mean dose to femoral heads was also reduced when compared with the 4-field technique. Conclusion: VMAT has an edge over other techniques in terms of target coverage and sparing of critical organs in the presence of metallic prosthesis. Information about the geometry and density of prosthesis will be beneficial for treatment planning.

Immunotherapy in advanced non-small-cell lung cancer (NSCLC) after progression on chemotherapy: real-world results from a prospective institutional cohort.

Objective: To analyze the outcomes of patients receiving immunotherapy (IO) with advanced non-driver mutated non-small-cell lung cancer (NSCLC) after progression on systemic treatment. Methods: The overall survival (OS), progression-free survival (PFS) and best response to IO of 64 patients who met our inclusion criteria were analyzed. Results: Median follow-up, OS and PFS were 35.9, 7.1 and 3.2 months, respectively. On uni- and multi-variable analysis, better ECOG PS and fewer extra-thoracic metastases were associated with prolonged OS and PFS. Response to IO was associated with prolonged OS, while thoracic radiotherapy and isolated CNS involvement were associated with prolonged PFS. ECOG PS, thoracic radiotherapy and PDL1 status significantly influenced the likelihood of response to IO. Overall, 30% patients experienced any grade toxicity. Conclusion: Our results are concordant with reported trial outcomes and support the application of IO in Indian patients.

Several clinical trials have demonstrated favorable results with immunotherapy in patients with lung cancer who do not have a mutation in their tumors. However, clinical trials are often designed to provide the best chance for a trial drug/intervention to demonstrate effectiveness. Therefore, they usually include relatively healthier patients compared to what clinicians see in their practice. To demonstrate the efficacy of a drug outside a clinical trial, a real-world analysis is performed, which is reported in this article. We analyzed lung cancer patients treated with immunotherapy at our institution and found comparable efficacy to reported clinical trials. This was important because the trials did not include any patients from our country. We also found that patients with fewer sites of involvement outside the lung and those who received radiotherapy to the lung (either during or before receiving immunotherapy) survived longer without disease progression.

Dosimetric Influence of Acuros XB Dose-to-Medium and Dose-to-Water Reporting Modes on Carcinoma Cervix Using Intensity-Modulated Radiation Therapy and Volumetric RapidArc Technique.

Aim: We aimed to evaluate the dosimetric influence of Acuros XB (AXB) dose-to-medium (Dm) and dose-to-water (Dw) reporting mode on carcinoma cervix using intensity-modulated radiation therapy (IMRT) and RapidArc (RA) technique. Materials and Methods: A cohort of thirty patients cared for carcinoma cervix was retrospectively selected for the study. Plans were computed using analytical anisotropic algorithm (AAA), AXB-Dm, and AXB-Dw algorithms for dosimetric comparison. A paired t-test and Pitman-Morgan dispersion test were executed to appraise the difference in mean values and the inter-patient variability of the differences. Results: The dose-volume parameters were higher for AXB-Dw in contrast to AAA for IMRT and RA plans, excluding D98%, minimum dose to planning target volume (PTV) and rectum mean dose (RA). There was no systematic trend observed in dose-volume parameters for PTV and organs at risk (OARs) between AXB-Dm and AXB-Dw for IMRT and RA plans. The dose-volume parameters for target were higher for AXB-Dm in comparison to AAA in IMRT and RA plans, except D98% and minimum dose to PTV. Analysis envisaged less inter-patient variability while switching from AAA to AXB-Dm in comparison to those switching from AAA to AXB-Dw. Conclusions: The present study reveals the important difference between AAA, AXB-Dm, and AXB-Dw computations for cervix carcinoma using IMRT and RA techniques. The inter-patient variability and systematic difference in dose-volume parameters computed using AAA, AXB-Dm, and AXB-Dw algorithms present the possible impact on the dose prescription to PTV and their relative constraints to OARs for IMRT and RA techniques. This may help in the decision-making in clinic while switching from AAA to AXB (Dm or Dw) algorithm for cervix carcinoma using IMRT and RA techniques.

Feasibility of Monte-Carlo algorithm in comparison with collapse-cone dose calculation algorithm of a commercial treatment planning system in the presence of high-density metallic implant: a dosimetric study.

BACKGROUND: The number of people with implanted hip prosthesis has grown worldwide. For radiotherapy planning of patients with hip implants, few main challenges are encountered. The aim of the present study was to evaluate the feasibility of different planning algorithms in the presence of high-density metallic implant in the treatment of patients with carcinoma cervix. RESULTS: It was found that D98% were 44.49 ± 0.11, 44.51 ± 0.13, 44.39 ± 0.22, and 44.45 ± 0.16 Gy for 4FMC6MV (4-field technique calculated with Monte-Carlo algorithm and 6 MV photon energy), 4FMC6MV_WP (4-field technique calculated with Monte-Carlo algorithm and 6 MV photon energy without prosthesis), 4FCC6MV (4-field technique calculated with collapse-cone-convolution algorithm and 6 MV photon energy), and 4FCC6MV_WP (4-field technique calculated with collapse-cone-convolution algorithm and 6 MV photon energy without prosthesis) respectively. Similarly, D2% were 49.40 ± 0.84, 49.05 ± 0.76, 48.97 ± 0.91, and 48.57 ± 0.85 Gray (Gy) for 4FMC6MV, 4FMC6MV_WP, 4FCC6MV, and 4FCC6MV_WP respectively. The present study has not suggested any major difference between the Monte-Carlo (MC) and collapse-cone-convolution (CCC) calculation algorithm in the presence of high-Z metallic implants. Volume of bowel receiving 15 Gy dose has shown a significant difference with prosthesis cases. This study investigates that hip prosthesis creates considerable changes in the treatment planning of cervical malignancies. CONCLUSION: CCC algorithm is in good agreement with MC calculation algorithm in the presence of high-density metallic implants in terms of target coverage and avoidance organ sparing except few parameters.

Plan quality assessment of modern radiotherapy delivery techniques in left-sided breast cancer: an analysis stratified by target delineation guidelines.

OBJECTIVE: This study compares planning techniques stratified by consensus delineation guidelines in patients undergoing whole-breast radiotherapy based on an objective plan quality assessment scale. METHODS: 10 patients with left-sided breast cancer were randomly selected, and target delineation for intact breast was performed using Tangent (RTOG 0413), ESTRO, and RTOG guidelines. Consensus Plan Quality Metric (PQM) scoring was defined and communicated to the physicist before commencing treatment planning. Field-in-field IMRT (FiF), inverse IMRT (IMRT) and volumetric modulated arc therapy (VMAT) plans were created for each delineation. Statistical analyses utilised a two-way repeated measures analysis of variance, after applying a Bonferroni correction. RESULTS: Total PQM score of plans for Tangent and ESTRO were comparable for FiF and IMRT techniques (FiF vs IMRT for Tangent, p = 0.637; FiF vs IMRT for ESTRO, p = 0.304), and were also significantly higher compared to VMAT. Total PQM score of plans for RTOG revealed that IMRT planning achieved a significantly higher score compared to both FiF and VMAT (IMRT vs FiF, p < 0.001; IMRT vs VMAT, p < 0.001). CONCLUSIONS: Total PQM scores were equivalent for FiF and IMRT for both Tangent and ESTRO delineations, whereas IMRT was best suited for RTOG delineation. ADVANCES IN KNOWLEDGE: FiF and IMRT planning techniques are best suited for ESTRO or Tangent delineations. IMRT also yields better results with RTOG delineation.

Malignant esophagorespiratory fistulas: a comparative effectiveness survival analysis.

OBJECTIVES: To analyse the survival of patients with malignant esophagorespiratory fistulas (ERF) and perform a comparative effectiveness analysis of ERF-directed interventions. METHODS: Fifty-five patients met our inclusion criteria, and data on ERF-directed interventions (stent placement, surgical repair and best supportive care) and their outcomes, along with clinical and treatment details, were recorded. The primary endpoints were overall survival (OS) and survival after developing ERF (F-OS). RESULTS: The median OS and F-OS for the entire cohort was 299 days (SE=23.2) and 123 days (SE=11.63), respectively. On univariable analysis, the American Joint Committee on Cancer (AJCC) stage (I-III vs IV) influenced both OS (403 vs 171 days; p=0.006) and F-OS (129 vs 67 days; p=0.034). Proximal location of ERF influenced OS favourably (494 vs 285 days; p=0.021), whereas patients developing ERF late in their disease course experienced inferior F-OS (96 vs 232 days; p=0.03). On multivariable analysis, the AJCC stage (IV vs I-III, HR=3.03 (1.41-6.50)), time to developing ERF from diagnosis (greater than vs within 3 months, HR=5.82 (1.84-18.36)) and location of ERF (distal vs proximal, HR=2.47 (1.14-5.34)) had a significant impact on F-OS. The comparative efficacy (OS and F-OS) of best supportive care was statistically equivalent to any intervention irrespective of AJCC stage and success/failure of initial or subsequent intervention(s). CONCLUSIONS: The survival of patients with ERF is dismal, and our analysis suggests that best supportive care results in equivalent OS and F-OS when compared with any intervention.

Primary angiosarcoma of the breast: a radiation oncologist's perspective with a concise review of the literature.

A 28-year-old premenopausal woman presented with a painful rapidly growing mass in her right breast and was evaluated with a core needle biopsy, which was suggestive of poorly differentiated carcinoma. Immunohistochemical evaluation revealed primary angiosarcoma of breast. Whole body 18flouro-deoxyglucose positron emission tomography CT showed few metabolically active soft tissue lesions in upper inner quadrant of right breast. The patient underwent breast conservation surgery and in view of positive surgical margins, received adjuvant radiation therapy. Post-treatment completion, the patient has been disease free for 6 months. Primary angiosarcoma of the breast is a rare malignancy which is best managed with a surgery as first approach, with due importance being given to the patient's perspective on their disease and choices for adjuvant treatment. Decisions in addition to adjuvant radiotherapy need to be made in the multidisciplinary clinic, due to paucity of data.

Image-guided volumetric modulated arc therapy (IG-VMAT) for unresectable ACC of the trachea: a feasible curative option.

A middle-aged man presented with progressively worsening breathlessness and non-productive cough for the last 3 months. On examination, his breathing was stridulous and air entry was decreased bilaterally. He underwent emergency fibre-optic bronchoscopy, which revealed a tracheal growth causing luminal narrowing, and after tumour debulking, he improved symptomatically. Histopathological evaluation of the specimen revealed an adenoid cystic carcinoma of the trachea, and systemic evaluation revealed metastatic dissemination. Systemic molecular-targeted therapy was initiated (gefitinib and later imatinib mesylate) and continued for 5 years, in view of stable disease on periodic follow-up. He subsequently presented with breathlessness again, which was managed with an emergency tracheostomy. In view of stable systemic disease and local progression only, he received definitive radiotherapy with image-guided volumetric modulated arc therapy, which resulted in a complete radiological response. The patient has been disease-free for the last 9 months.