Cardiac markers in left-sided breast cancer patients receiving adjuvant radiotherapy: a prospective study.

OBJECTIVES: To investigate the association between radiotherapy (RT) and cardiac biomarkers in women with left-sided breast cancer. METHODS: This prospective observational study recruited patients with stage I-III left-sided breast cancer without coronary heart disease who required adjuvant RT. High-sensitivity troponin I(hsTnI), N-terminal pro-brain natriuretic peptide(NT-proBNP), and high-sensitivity C-reactive protein(hsCRP) levels were measured pre-RT, immediately after RT, and 3 months post-RT. Cardiac-sparing RT techniques were utilized (Field-in-Field IMRT/VMAT ± voluntary deep inspiration breath-hold). Statistical analyses were performed using non-parametric tests and multivariable quantile regression (QR). RESULTS: One hundred five patients completed the study, with 63 evaluable at three months post-RT. Pre- and post-RT biomarkers showed no significant differences. Median pre-RT and post-RT values were: hsTnI (0.012ng/mL; 0.012ng/mL), hsCRP (3.1 mg/L; 2.8 mg/L), and NT-proBNP (59pg/mL; 45pg/mL). Three months post-RT, hsTnI, hsCRP and NT-proBNP levels also showed no significant differences. Multivariable QR revealed no association between heart Dmean [median(IQR): 2.87 Gy (2.05-3.94)] and post-RT biomarkers. Age and BMI were associated with hsCRP and NT-proBNP, respectively. CONCLUSIONS: hsTnI, NT-proBNP, and hsCRP are not correlated with contemporary low cardiac exposure in left-sided breast cancer patients treated with contemporary RT techniques.

Is it too early to recommend local treatment in oligometastatic non-small cell lung cancer: a plea for equipoise.

Oligometastatic non-small cell lung cancer (OMD NSCLC) has been proposed to bridge the spectrum between non-metastatic and widely metastatic states and is perceived as an opportunity for potential cure if removed. Twelve clinical trials on local treatment have been reported, yet none are conclusive. These trials informed the development of a joint clinical practice guideline by the American & European Societies for Radiation Oncology, which endorses local treatment for OMD NSCLC. However, the heterogeneity between prognostic factors within these trials likely influenced outcomes and can only support guidance at this time. Caution against an uncritical acceptance of the guideline is discussed, as strong recommendations are offered based on expert opinion and inconclusive evidence. The guideline is also examined by a patient's caregiver, who emphasizes that uncertain evidence impedes shared decision making.

Intuitive evaluation of contemporary management strategies in thymoma - the largest Indian experience.

Background: The aim was perusal of the treatment strategies, clinical outcomes and factors impacting these outcomes in thymoma. Materials and methods: A total of 119 patients diagnosed and treated cases of thymoma, at our hospital, were taken for analysis. Thirty-one patients were excluded due to inadequate medical records. Descriptive statistics were used to report demographic and clinical characteristics. Time period between diagnosis and death was defined as overall survival (OS). Multivariate analysis (MVA), using cox regression modelling, was done by including clinicopathological factors in a bid to identify prognostic factors influencing OS. SPSS version 26 was used for statistical analysis. Results: The mean age of the patients was 52.17 years and 39 (44.3%), 19 (21.6%), 17 (1.3%) and 13 (4.8%) patients presented with Masaoka stage II, IV, III and I, respectively. Surgery was done in 64 (72.7%) of the patients as a part of the treatment strategy. Radiotherapy was administered to a total of 57 patients with a median dose of 50.4 Gy. Early Masaoka stage at presentation and use of surgery in the treatment plan were statistically significant prognostic factors for a better overall survival on multivariate analysis. Conclusion: Judicious use of radiotherapy and chemotherapy in locally advanced cases may render them resectable. In a bid to gain good survival rates, aggressive multimodality treatment should be offered to the patients.

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.

Treatment Delay during Radiotherapy of Cancer Patients due to COVID-19 Pandemic.

PURPOSE: To analyze the impact of treatment delay caused by COVID-19 infection on patients scheduled for radiotherapy treatment. METHODS AND MATERIALS: In this descriptive study, we analyzed all patients who were COVID-19 positive during the scheduled radiotherapy course, those who had an infection while on neoadjuvant treatment period, or during surgery before the start of radiation. The study period was from June 2020 to May 2021. A treatment delay was defined as a delay in starting the radiation treatment, a gap during their scheduled radiation treatment, or treatment discontinuation. All patients who had a treatment delay were followed-up till November 2021. RESULTS: The median follow-up time of the study was 13 months. Ninety-four patients were selected for the study who met the inclusion criteria. Seventy-seven patients had a mild COVID-19 infection, while 17 had a moderate to severe illness. Of the entire cohort, 83 patients had a treatment delay. The median treatment delay (MTD) in days was 18 (6 to 47). Amongst those who had a treatment delay, 66 patients were treated with curative intent, of which 51 patients are on follow-up - 34 patients are disease-free (MTD - 18.5, 10 to 43), seven had either a residual disease or locoregional recurrence (MTD - 22, 10 to 32), seven had distant metastasis (MTD - 18, 15 to 47), and three patients died (MTD - 20, 8 to 27). Of three patients who died, only one died of COVID-19-related causes. CONCLUSIONS: Even though the mortality due to COVID-19 infection among those who underwent radiotherapy was low, a treatment delay might have caused adverse treatment outcomes. Longer follow-up of these patients is required to further establish this. It will remain debatable whether it was worth delaying radiotherapy for mild to moderate COVID-19 infection for a significant time to cause a potential cancer treatment failure.

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.

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.

Impact of acuros XB algorithm in deep-inspiration breath-hold (DIBH) respiratory techniques used for the treatment of left breast cancer.

AIM: To investigate the impact of Acuros XB (AXB) algorithm in the deep-inspiration breath-hold (DIBH) technique used for treatment of left sided breast cancer. BACKGROUND: AXB may estimate better lung toxicities and treatment outcome in DIBH. MATERIALS AND METHODS: Treatment plans were computed using the field-in-field technique for a 6 MV beam in two respiratory phases - free breathing (FB) and DIBH. The AXB-calculations were performed under identical beam setup and the same numbers of monitor units as used for AAA-calculation. RESULTS: Mean Hounsfield units (HU), mass density (g/cc) and relative electron density were -782.1 ±â€¯24.8 and -883.5 ±â€¯24.9; 0.196 ±â€¯0.025 and 0.083 ±â€¯0.032; 0.218 ±â€¯0.025 and 0.117 ±â€¯0.025 for the lung in the FB and DIBH respiratory phase, respectively. For a similar target coverage (p > 0.05) in the DIBH respiratory phase between the AXB and AAA algorithm, there was a slight increase in organ at risk (OAR) dose for AXB in comparison to AAA, except for mean dose to the ipsilateral lung. AAA predicts higher mean dose to the ipsilateral lung and lesser V20Gy for the ipsilateral and common lung in comparison to AXB. The differences in mean dose to the ipsilateral lung were 0.87 ±â€¯2.66 % (p > 0.05) in FB, and 1.01 ± 1.07% (p < 0.05) in DIBH, in V20Gy the differences were 1.76 ±â€¯0.83% and 1.71 ±â€¯0.82% in FB (p < 0.05), 3.34 ± 1.15 % and 3.24 ± 1.17 % in DIBH (p < 0.05), for the ipsilateral and common lung, respectively. CONCLUSION: For a similar target volume coverage, there were important differences between the AXB and AAA algorithm for low-density inhomogeneity medium present in the DIBH respiratory phase for left sided breast cancer patients. DIBH treatment in conjunction with AXB may result in better estimation of lung toxicities and treatment outcome.

A case report evaluating combined effect of intensity-modulated radiotherapy and deep inspiratory breath-hold for mediastinal lymphoma: A dosimetric analysis.

Excellent survival has been reported after combined modality treatment in bulky mediastinal Hodgkin's lymphoma. Late effects such as cardiac morbidity and secondary cancers have been reported after radiotherapy (RT), especially in young adults. Advanced RT techniques such as deep inspiratory breath-hold (DIBH), intensity-modulated RT (IMRT), and volumetric arc therapy have been used recently to reduce these late effects with encouraging results. We hereby present a case report evaluating combined effect of DIBH and IMRT in a young adult with mediastinal lymphoma.

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.

Nodal volume as a prognostic factor in locally advanced head and neck cancer: Identifying candidates for elective neck dissection after chemoradiation with IGRT from a single institutional prospective series from the Indian subcontinent.

OBJECTIVE: Nodal volume as a prognostic factor has been extensively evaluated in head and neck cancer, however there is still no consensus. We attempted to analyze nodal volume as a prognostic factor in head and neck cancer treated with chemoradiation (CCRT) without an elective neck dissection with image guided intensity modulated radiotherapy (IG-IMRT). MATERIAL AND METHODS: We prospectively analysed 87 patients of Stage III-IV cancer of the oropharynx (57), and hypopharynx (30), who subsequently received definitive concurrent chemoradiation. Total Nodal volume (TNV) was the sum of all lymph node volumes calculated by volume algorithm from the planning CT. The impact of TNV on overall survival (OS) & regional control (RC) was assessed. Survival analysis was done using SPSS version 20.0 (SPSS, Chicago, Illinois). A receiver operating characteristics (ROC) curve analysis was done for estimation of cut offs. RESULTS: The 2 year OS & RC were 64% and 83% respectively. On multivariate analysis, the TNV was a significant prognostic factor for OS &RC. ROC curve analysis found an optimal volumetric cut off of 15cc for OS & RC. The 2 year OS & RC for <15cc/>15cc group were 78% /30% (p = 0.001) & 100%/52% (p = 0.001). Similar results were obtained on subset analysis of our oropharyngeal patients with 2 year OS 75%/24% for the <15cc and >15cc group (p = 0.001). CONCLUSION: TNV is an independent prognostic factor for OS & RC in head and neck cancer. TNV can identify patients for consideration of elective neck dissection post CCRT ie for patients with TNV > 15CC.

Simultaneous integrated boost by Intensity Modulated Radiotherapy (SIB-IMRT) in patients undergoing breast conserving surgery - A clinical and dosimetric perspective.

AIM: To study feasibility of simultaneous integrated boost by intensity modulated radiotherapy (SIB-IMRT) in patients undergoing breast conserving surgery and its impact on cosmesis and dosimetry. PATIENTS AND METHODS: Between January 2014 and June 2017, all breast cancer patients fulfilling inclusion and exclusion criteria were enrolled in a prospective study conducted at a tertiary cancer centre in North India. All patients received adjuvant radiotherapy by simultaneous integrated boost technique following breast conserving surgery. Clinical information including patient and pathological characteristics, observed acute and chronic toxicities along with cosmesis using Harvard score were recorded and analysed. Univariate analysis and multivariate logistic regression analysis were performed for those variables which were found to be significant (p < 0.050) to study the influence of clinicopathological and dosimetric factors on toxicity and cosmetic outcome. RESULTS: Maximum acute skin toxicity during treatment was Grade 0-1 in 68.2% and Grade 2-3 in 31.8% of cases, respectively. Fibrosis was the commonest late toxicity with ≥Grade II fibrosis being noted in 16.3% of cases. Assessment of global cosmesis at 12 months follow-up showed good/excellent cosmesis in 88.4% of cases. Mean age, tumor size and homogeneity index (HI) were the significant factors associated with fair or poor cosmetic outcome and ≥Grade 2 fibrosis on multivariate analysis. Telengectasia and breast edema were more frequent in patients with larger tumor size/GTV volume. There were 5 recurrences including 1 ipsilateral local breast tumor recurrence. CONCLUSION: SIB-IMRT is a dosimetrically feasible option in patients undergoing breast conserving surgery and provides good/excellent cosmetic outcome.

Early Clinical Outcomes, Patterns of Failure, and Acute Haematologic Toxicity of Image-Guided Volumetric Modulated Arc Therapy (IG-VMAT) in the Definitive Treatment of Locally Advanced Carcinoma Cervix.

PURPOSE: To evaluate clinical outcomes and failure patterns in patients with locally advanced cervical cancer (LACC) treated definitively using image-guided volumetric-modulated arc therapy (IG-VMAT). METHODS AND MATERIALS: This retrospective review included 18 consecutively treated patients with LACC. Treatment consisted of IG-VMAT and concurrent chemotherapy followed by intracavitary radiotherapy. The primary end points were overall survival (OS) and disease-free survival (DFS). Acute haematologic toxicity was evaluated using Radiation Therapy Oncology Group (RTOG) criteria. RESULTS: A total of 16 patients were either stage IIB or IIIB and the median follow-up was 30.5 months (interquartile range: 13-36.25 months). The 2-year DFS was 63.3% (95% confidence interval [CI]: 52.8%-72.4%) and 2-year OS was 72.2% (95% CI: 62.1%-80.5%). There were 7 treatment failures, predominantly in-field. Acute haematologic toxicity was low. CONCLUSIONS: IG-VMAT is associated with favourable outcomes for patients with LACC.