Long-term follow-up in high-grade meningioma and outcome analysis.

Objectives: The determinants of progression-free survival (PFS) and overall survival (OS) for higher-grade meningiomas have not been clearly established and to summarize the long-term clinical outcome for patients with grade 2 or 3 meningioma and assess the PFS and OS factors. Materials and Methods: The study included all individuals, who had undergone surgical removal of cerebral meningiomas between 2005 and 2020 and whose histological results suggested a World Health Organization (WHO) grade 2 or grade 3 diseases. Kaplan-Meier curves are plotted to examine tumor control and OS after the follow-up. The reverse Wald logistic regression and Mantel-Cox test were used in multivariate analysis for tumor recurrence and mortality. Results: There were 94 individuals enrolled with 82 having WHO grade 2 tumors and 12 having WHO grade 3 lesions. Gross total resection of the tumor was present in 73 patients (78%), and adjuvant radiotherapy (RT) was administered to 43 (45.7%) individuals. During the course of the study, 17 patients died. The WHO grade of the tumor, the extent of resection, and the absence of bone involvement were all independent predictors of better survival in a multivariate analysis. Furthermore, whereas adjuvant RT after surgery enhanced survival, it was not statistically significant (hazard ratios [95% confidence interval CI] = 1.91 [0.15-23.52] [P = 0.61]). Conclusion: The degree of tumor excision is the strongest predictor of PFS and OS. In the event of a recurrence, rather than opting for upfront radiation, a second surgery with the goal of maximum safe resection should be performed.

Cholangiocarcinoma: Recent Advances in Molecular Pathobiology and Therapeutic Approaches.

Cholangiocarcinomas (CCA) pose a complex challenge in oncology due to diverse etiologies, necessitating tailored therapeutic approaches. This review discusses the risk factors, molecular pathology, and current therapeutic options for CCA and explores the emerging strategies encompassing targeted therapies, immunotherapy, novel compounds from natural sources, and modulation of gut microbiota. CCA are driven by an intricate landscape of genetic mutations, epigenetic dysregulation, and post-transcriptional modification, which differs based on geography (e.g., for liver fluke versus non-liver fluke-driven CCA) and exposure to environmental carcinogens (e.g., exposure to aristolochic acid). Liquid biopsy, including circulating cell-free DNA, is a potential diagnostic tool for CCA, which warrants further investigations. Currently, surgical resection is the primary curative treatment for CCA despite the technical challenges. Adjuvant chemotherapy, including cisplatin and gemcitabine, is standard for advanced, unresectable, or recurrent CCA. Second-line therapy options, such as FOLFOX (oxaliplatin and 5-FU), and the significance of radiation therapy in adjuvant, neoadjuvant, and palliative settings are also discussed. This review underscores the need for personalized therapies and demonstrates the shift towards precision medicine in CCA treatment. The development of targeted therapies, including FDA-approved drugs inhibiting FGFR2 gene fusions and IDH1 mutations, is of major research focus. Investigations into immune checkpoint inhibitors have also revealed potential clinical benefits, although improvements in survival remain elusive, especially across patient demographics. Novel compounds from natural sources exhibit anti-CCA activity, while microbiota dysbiosis emerges as a potential contributor to CCA progression, necessitating further exploration of their direct impact and mechanisms through in-depth research and clinical studies. In the future, extensive translational research efforts are imperative to bridge existing gaps and optimize therapeutic strategies to improve therapeutic outcomes for this complex malignancy.

Meningeal Melanocytoma- A Clinicohistological Masquerader.

Meningeal melanocytoma is a rare benign tumor, most frequently located in the posterior fossa and spinal canal. Localized tumors present as leptomeningeal masses and range from well-differentiated melanocytomas to lesions of intermediate malignancy and overtly malignant melanomas. Spinal meningeal melanocytoma has a benign course and is amenable for gross total resection. The outcome is favorable following complete resection. Meningeal melanocytoma may occasionally be associated with histological benign leptomeningeal spread and aggressive clinical course in spite of the absence of malignant transformation. We report a case of intraspinal melanocytoma in a 57-year-old female, which clinically as well as radiologically mimicked other spinal lesions. The final diagnosis was confirmed on histopathology.

A Pilot Study of Perioperative Cisplatin-Capecitabine Chemotherapy With Preoperative Chemoradiation for Resectable Gastric Cancers.

OBJECTIVES: The standard of care for resectable gastric cancers (GCs) includes perioperative chemotherapy (CT) or postoperative chemo/chemoradiotherapy (CRT) strategies. Poor treatment compliance postsurgery suggests that intensified surgical adjuvant treatment is more likely deliverable preceding surgery and, therefore, the safety and efficacy of perioperative cisplatin-capecitabine (CX) with preoperative chemoradiation (preopCRT) were ascertained. MATERIALS AND METHODS: Between January 2017 and December 2018, 28 potentially resectable locally advanced GC patients were offered neoadjuvant CT-2 cycles of CX at 3-weekly intervals, followed by preopCRT 45 Gy/25 fractions/5 weeks and concurrent capecitabine, followed by surgical resection and 3 adjuvant cycles of CX. RESULTS: Neoadjuvant CT was commenced in 28 patients (100%), preopCRT in 18 patients (64%), and surgery performed in 13 patients (46%). At each treatment step, decreasing patient numbers were due mainly to disease progression (12 [43%]) or other reasons, including (3 [11%]) from treatment-related toxicity. The R0 resection rate was 92% (12/13); a median of 18 nodes was obtained after D2 nodal clearance in 92% (12/13). There were 20%/4%/4% grade 3/4/5 toxicities. The median radiotherapy dose/duration was 45 Gy/5.4 weeks. Adjuvant CT was started in 11 patients (39%) and the third cycle was received by 7 patients (25%). No tumor (ypT0N0) was noted in 23% of the operated patients (3/13), or 11% of the intention-to-treat population (3/28). The median, 1-year, and 2-year survivals were 12 months, 53%, and 32%, respectively. CONCLUSIONS: Intensified preoperative treatment is doable in relatively unselected advanced GC patients in real-world settings of a public-sector hospital from a low-middle-income country. Disease progression during preoperative therapy allows patients destined for early clinical evidence of disease dissemination to avoid futile surgery, as opposed to a surgery-first strategy, without an overt increase in surgical morbidity or mortality, with encouraging R0 resection rates.

Optimal Standardized Uptake Value Threshold for Auto contouring of Gross Tumor Volume using Positron Emission Tomography/Computed Tomography in Patients with Operable Nonsmall-Cell Lung Cancer: Comparison with Pathological Tumor Size.

PURPOSE: Incorporating 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG-PET/CT) for gross tumor volume (GTV) delineation is challenging due to varying tumor edge based on the set threshold of the standardized uptake value (SUV). This study aims to determine an optimal SUV threshold that correlates best with the pathological tumor size. MATERIALS AND METHODS: From January 2013 to July 2014, 25 consecutive patients of operable nonsmall-cell lung cancer (NSCLC) who underwent staging18F-FDG-PET/CT before surgical resection were included in the test cohort and 12 patients in the validation cohort. GTVs were delineated on the staging PET/CT by automatic delineation using various percentage threshold of maximum SUV (SUVmax) and absolute SUV. The maximum pathological tumor diameter was then matched with the maximum auto-delineated tumor diameter with varying SUV thresholds. First-order linear regression and Bland-Altman plots were used to obtain an optimal SUV threshold for each patient. Three radiation oncologists with varying degrees of experiences also delineated GTVs with the visual aid of PET/CT to assess interobserver variation in delineation. RESULTS: In the test set, the mean optimal percentage threshold for GTV was SUVmax of 35.6%±18.6% and absolute SUV of 4.35 ± 1.7. In the validation set, the mean optimal percentage threshold SUV and absolute SUV were 36.9 ± 16.9 and 4.1 ± 1.6, respectively. After a combined analysis of all 37 patients, the mean optimal threshold was 36% ± 17.9% and 4.27 ± 1.7, respectively. Using Bland-Altman plots, auto-contouring with 40% SUVmax and SUV 4 was in greater agreement with the pathological tumor diameter. CONCLUSION: Automatic GTV delineation on PETCT in NSCLC with percentage threshold SUV of 40% and absolute SUV of 4 correlated best with pathological tumor size. Auto-contouring using these thresholds will increase the precision of radiotherapy contouring of GTV and will save time.

Cardiac dose reduction using deep inspiratory breath hold (DIBH) in radiation treatment of left sided breast cancer patients with breast conservation surgery and modified radical mastectomy.

PURPOSE: Deep inspiration breath hold (DIBH) reduces heart and pulmonary doses during left-sided breast radiation therapy (RT); however, there is limited information whether the reduction in doses is similar in patients with modified radical MRM (MRM) and breast conservation surgery (BCS). The primary objective was to determine whether DIBH offers greater dosimetric reduction in cardiac doses in patients with MRM as compared to BCS with secondary objectives of documenting time consumed in counseling, simulation and planning such techniques. METHODS: Thirty patients with diagnosis of left sided breast cancer underwent CT simulation both free breathing (FB) and DIBH. Patients were grouped into two cohorts: MRM (n = 20) and BCS (n = 10). 3D-conformal plans were developed and FB was compared to DIBH for entire group (n = 30) and each cohort using Wilcoxon signed-rank tests for continuous variables and McNemar's test for discrete variables. The percent relative reduction conferred by DIBH in mean heart (Dmean heart) and left anterior descending artery dose (LADmean and LADmax), heart V25,V10, V2 and ipsilateral DmeanLung,V20, V12 were compared between the two cohorts using Wilcox rank-sum testing. A two-tailed p-value ≤ 0.05 was considered statistically significant. Time consumed during FB and DIBH from patient counseling to planning was documented. RESULTS: Patients undergoing BCS had comparable boost target coverage on DIBH and FB. For the overall group (n = 30), DIBH reduced Dmean heart and LAD dose, V25, V10 and V2 doses for the heart and Ipsilateral DmeanLung, V20, V12 which was statistically significant. For individual cohorts DIBH did not significantly reduce the lung (Ipsilateral DmeanLung, V20, V12) and LAD (LADmean and LADmax) doses for BCS while significant reduction in all cardiopulmonary doses was seen in MRM cohort. Despite significant reductions with DIBH in MRM, ipsilateral lung constraint of V12 < 15% was less commonly achieved in MRM (n = 11, 55%) requiring nodal radiation as compared to BCS (n = 3, 30%). Percent reduction in all cardiac and pulmonary dosimetric parameters with DIBH was similar in the MRM cohort as compared to BCS cohort. In total 73.1 ± 2.6 min was required for FB as compared to 108.1 ± 4.1 min in DIBH. CONCLUSION: DIBH led to significant reduction of cardiac doses in both MRM and BCS. Reduction of lung and LAD doses were significant in MRM cohort. All cardiac constraints were met with DIBH in both cohorts, lung constraints were less frequently met in MRM cohort requiring nodal radiation.

Comparative retrospective analysis of locoregional recurrence in unselected breast cancer patients treated with conventional versus hypofractionated radiotherapy at a tertiary cancer center?

BACKGROUND: Role of hypofractionated radiotherapy (HFRT) in early breast cancer is established; comparatively, there are limited data for HFRT in locally advanced breast cancer (LABC). We report the impact of HFRT in unselected breast cancer patients in comparison with historically treated patients with conventional fractionated radiotherapy (CFRT). PATIENTS AND METHODS: Records of 463 breast cancer patients treated between January 09 and July 13 with CFRT (50 Gy/25 fr) or HFRT (42.4 Gy in 16 fractions or 40 Gy in 15 fractions) in two sequential periods were retrospectively reviewed. The analysis was done in August 2018. The primary endpoint was to compare the differences in locoregional recurrence rate. RESULTS: Of the 463 patients, 209 received CFRT and 254 received HFRT. The median age was 48 years (interquartile range: 40-56), premenopausal (CFRT: 23% vs. HFRT 39%, P = 0.005). The most common pathology was infiltrating ductal carcinoma (81%) with Grade III tumors (45%), estrogen receptor (+) was seen in 44%, triple-negative breast cancer in 34%, and Her2Neu (3+) were seen in 27%. Two hundred and fifty-four patients (54.5%) had undergone breast-conserving surgery (BCS) and 209 patients (45%) modified radical mastectomy (MRM). Nodal radiotherapy was delivered in 76% versus 64% in patients receiving CFRT versus HFRT, respectively (P = 0.005). With a median follow-up of 46 months in CFRT and 57 months in HFRT, 9/209 (4.3%) patients in CFRT and 7/254 (2.7%) in HFRT had locoregional relapse (LRR). The 4 years#39; actuarial local recurrence-free survival (LRFS) in CFRT versus HFRT was 95% versus 97% (P = 0.37). The mean estimated LRFS (local relapse-free survival) for CFRT is 113.4 months and for HFRT 94.2 months (P = 0.3). CONCLUSIONS: The risk of local recurrence among patients of breast cancer treated with HFRT after BCS or MRM was not worse when compared to CFRT.

Comparison of two hypofractionated radiotherapy schedules in locally advanced postmastectomy breast cancer patients.

INTRODUCTION: The role of hypofractionated radiotherapy (HFRT) in postmastectomy breast cancer patients is not well established. This study was done to establish the role of two different HFRT schedules in the treatment of chest wall and regional lymph nodes after mastectomy. MATERIALS AND METHODS: Between 2012 and 2016, consecutively registered patients of locally advanced breast cancer patients having undergone mastectomy and adjuvant radiotherapy (RT) at a tertiary cancer center were analyzed. Locoregional recurrence (LRR) was the primary endpoint, whereas overall survival (OS), disease-free survival (DFS), and both acute and late adverse events were secondary endpoints. RESULTS: A total of 34 patients who were treated with 39 Gy in 13 fractions over 2½ weeks and 35 patients who were treated with 40 Gy in 15 fractions over 3 weeks were identified. The median follow-up period was 47 months and 63.5 months in the 39 Gy and 40 Gy arms, respectively. LRR was seen in 11.8% and 8.6% of patients in the 39 Gy and 40 Gy arms, respectively. OS at 4 years was 66% and 71.5% in the 39 Gy and 40 Gy arms, respectively. The mean DFS for 39 Gy and 40 Gy arms was 43.6 months and 66.4 months, respectively (P = 0.822). Acute skin toxicity was similar in the two groups. Arm edema was significantly more in the 40 Gy arm. CONCLUSION: The two HFRT schedules are equivalent to each other in terms of survival outcomes. Arm edema is higher with 40 Gy arm as compared to 39 Gy arm.

Inflammatory Biomarkers, Hematopoietic Stem Cells, and Symptoms in Breast Cancer Patients Undergoing Adjuvant Radiation Therapy.

BACKGROUND: Fatigue and insomnia are common symptoms experienced by breast cancer patients undergoing adjuvant radiation therapy (RT), yet the underlying mechanisms of these symptoms are unclear. In particular, the roles of hematopoietic stem cells (HSCs) and inflammatory cytokines remain to be elucidated. METHODS: Breast cancer patients (n = 147) completed questionnaires to longitudinally assess symptoms before, during, and after adjuvant RT. Phlebotomies were performed prior to RT, at the second and fifth treatment fractions, end of treatment (EOT), and 1 month after completing RT, assessing for CD34+, CD45+, full hematology, and 17 inflammatory cytokines. The associations between symptoms and all biomarkers were evaluated. All statistical tests were 2-sided. RESULTS: General fatigue and insomnia worsened with RT, with peak levels observed at EOT, which remained statistically significant even after controlling for anxiety and depression (P < .05 for all). CD34+, CD45+, white blood cell, and lymphocyte counts decreased, with the lowest levels also observed at EOT (P < .001). Fatigue and insomnia were associated with changes in both interferon γ-induced protein 10 (IP-10) - (P = .03 and P = .01, respectively) and tumor necrosis factor receptor II (TNF-RII) (P = .02 and P = .006, respectively), while mental fatigue was associated with increased matrix metalloproteinases-2 (MMP-2) levels (P = .03). Patients who received prior chemotherapy demonstrated statistically significantly greater severity in all symptoms, with lower baseline HSC levels. CONCLUSIONS: This is the first longitudinal study to examine linkages between symptoms, HSCs, and cytokines, demonstrating that fatigue and insomnia shared associations with increasing serum levels of IP-10 and TNF-RII, and mental fatigue was associated with increasing serum levels of MMP-2. Our findings highlight opportunities for further research into mechanisms and potential interventions for these symptoms.

Patient-reported acute fatigue in elderly breast cancer patients treated with and without regional nodal radiation.

PURPOSE: Although regional nodal irradiation (RNI) improves outcomes in breast cancer (BC) patients, it is associated with increased toxicity. Therefore, controversy still exists surrounding its indications. The purpose of this study was to evaluate and compare patient-reported acute fatigue in elderly BC patients with and without regional nodal radiation (RNI). METHODS: Elderly breast cancer patients (≥ 65 years) treated with adjuvant radiotherapy (RT) between 2012 and 2017 were identified from a prospective database. The validated Edmonton Symptom Assessment System-revised (ESAS-r) questionnaire, which assesses fatigue, was completed prior to (baseline), during, at end of RT and first follow-up (3-6 months). Symptoms were rated on a 10-point Likert scale, with higher scores indicating higher fatigue. Patient's treatment characteristics were also recorded prospectively. This was a retrospective study which identified elderly breast cancer patients who had received adjuvant radiation, completed ESAS-r prospectively and provided research consent for using ESAS-r. Patients were divided into two cohorts: those who received RNI (cohort 1) and those who did not (cohort 2). A minimal clinically important difference (MID) was defined using an anchor of ≥ 1-point compared to baseline. The proportion of patients reporting a change in fatigue at the end of RT was evaluated. To test the robustness of the results, dynamic changes of fatigue scores over time were further compared between the cohorts using a general linear mixed model (GLMM) after assuming individual patient with random effect. Univariate and multivariable logistic regression were conducted to assess the association between RNI and MID after adjusting for potential confounders. In addition to longitudinal analysis, a multivariable mixed effect model was developed to determine the association of RNI with fatigue after adjusting for potential confounders. A two-tailed p value ≤ 0.05 was considered statistically significant. RESULTS: Of the 1198 patients, 859 had provided research consent and completed the ESAS-r at baseline and any other time-point and were included in the longitudinal analysis (cohort 1 = 159, cohort 2 = 700), while 637 (cohort 1 = 135, cohort 2 = 502) patients completed the ESAS-r at baseline and end of radiotherapy and were included in the anchor-based analysis. Mean age at diagnosis was similar between the groups: cohort 1; 71.5 ± 5.7 vs. cohort; 2 72 ± 5.4 years (total 71.8 ± 5.5). Overall, cohort 1 had higher stage (Stage 3: 32.7% vs 3.6%, p < 0.001) and reception of chemotherapy (68.6% vs. 16.1%, p < 0.001). Mean baseline fatigue was higher for cohort 1 vs. 2 (2.7 ± 2.5 vs. 2.1 ± 2.3, p = 0.006). On univariate and multivariable analyses, RNI was not associated with an increased odd of MID for fatigue at the end of RT (44% vs. 47%; OR 0.89, 95% CI 0.61-1.30, p = 0.56). After adjusting for confounders (age, duration of RT, endocrine therapy), treatment with RNI was not associated with increased odds of worse fatigue at the end of RT (OR 1.33, 95% CI 0.85-2.10, p = 0.22). Higher baseline fatigue (OR 0.86, 95% CI 0.79-0.92, p < 0.001) and receipt of chemotherapy had decreased odds (OR 0.50, 95% CI 0.32-0.86, p = 0.001) and were the only factors associated with decreased odds of MID. Dynamic changes showed a significant worsening of fatigue scores over time (p < 0.001) towards the end of RT and recovery at first follow-up (p < 0.001) with no difference between the cohorts (p = 0.38); both experienced parallel worsening of fatigue levels over time (cohort*time p = 0.71 and cohort*time2p = 0.78). On multivariable analysis earlier stage, the absence of chemotherapy and higher baseline depression were independent predictors of worse fatigue scores over time (p = 0.01, p = 0.003, and p = 0.02, respectively). CONCLUSION: The addition of RNI in elderly BC patients is not associated with a significant worsening of patient-reported fatigue. Predictors of acute fatigue will enable shared decision making between patients and clinicians.

Utilization patterns and temporal trends of internal mammary nodal irradiation at a tertiary cancer center.

PURPOSE: The role and uptake of internal mammary nodal irradiation (IMNI) is variable. This study was designed to quantify the rates and determinants of IMNI at a tertiary cancer center. METHODS: Consecutively treated breast cancer patients receiving adjuvant locoregional radiation therapy (RT) from January 1, 2012 to December 31, 2017 were sorted by IMNI receipt, disease risk and time period of RT delivery (2012-2015 vs 2016-2017). Differences between risk categories and groups were evaluated using χ2/Fisher's and Mann-Whitney test for categorical and continuous variables, respectively. Univariable and multivariable logistic regression analysis was done to determine factors associated with IMNI receipt. RESULTS: A total of 1566 patients were eligible, with 376 in Group 1 (IMNI), and 1190 in Group 2 (no IMNI). The proportion of patients receiving IMNI increased significantly each year (p < 0.0001), and 83% of patients receiving IMNI had pT1-2/pN1 disease. On univariable analysis, younger age, lymphovascular invasion, medial/central quadrant, higher stage, PR negative, mastectomy, axillary dissection, receipt of chemotherapy and nodal positivity had higher odds of IMNI. On multivariable analysis, younger age (p = < 0.001), medial/central quadrant (p = 0.0026), PR negative (p = 0.0011), mastectomy (p = 0.0055), increasing nodal positivity (p < 0.0001) and late cohort (p = 0.001) had increased likelihood of IMNI. The use of deep-inspiration breath hold was significantly higher in those receiving IMNI (45% vs 26%, p < 0.0001), and permitted achievement of acceptable mean heart and lung doses. CONCLUSIONS: There was a significant increase in IMNI utilization after 2015. Younger age, medial/central quadrant, PR-negative and node-positive disease predicted for receipt of IMNI. Modern RT techniques permit the safe delivery of IMNI.

Coverage with dosimetric concordance index (CDCI): a tool for evaluating dosimetric impact of inter-observer target variability in brachytherapy.

PURPOSE: The aim of this study was to propose an index for evaluating dosimetric impact of inter-observer target delineation variability in brachytherapy. MATERIAL AND METHODS: The coverage with dosimetric concordance index (CDCI) is expressed as CDCIcommon and CDCIpair. The CDCIcommon is the mean coverage of target volume with common volume irradiated by prescription dose among all observers and represents the condition of worst target coverage. CDCIpair is the generalized form of CDCI, which is mean target coverage with common prescription volume obtained between all possible pairs of observers and represents more realistic coverage of target with dosimetric concordance. The index was used to evaluate the dosimetric impact of target delineation variability in optimized conformal plans on target volumes of five radiation oncologists for twenty patients of multi-catheter interstitial partial breast brachytherapy. RESULTS: The mean decline of 5.6 ±3.2% and 11.3 ±5.7% in CDCIpair and CDCIcommon, respectively, was observed comparing to coverage index (CI) of target volume in all patients due to inter-observer target variability. CDCIcommon and CDCIpair were found to have significant linear correlation (r = 0.964, p < 0.000). The difference between CDC and CI increased with the mean relative target volume among observers. Significant correlation (r = 0.962, p < 0.000) was also noted for the difference (Δ) in CDCIcommon and CDCIpair with CI of target volume. CONCLUSIONS: The recommended indices and difference between the dosimetric coverage of target volume (CI) with CDCI (ΔCDCI) can be used for evaluating dosimetric impact of the inter-observer target delineation variability.

Impact of inter-observer variations in target volume delineation on dose volume indices for accelerated partial breast irradiation with multi-catheter interstitial brachytherapy.

PURPOSE: To investigate dosimetric impact of inter-observer variation in clinical target volume(CTV) delineation for patients undergoing interstitial partial breast brachytherapy. METHODS: Five radiation oncologists delineated CTV in twenty patients who underwent multi-catheter partial breast brachytherapy. Five treatment plans for each patient were graphically optimized for CTV of all observers and evaluated using coverage index(CI), external volume index(EI), overdose volume index(OI) and conformal index(COIN). In addition, volume enclosed by prescription isodose(V100), its spatial concordance(CIcommon), mean coverage of all CTVs with common volume of prescription dose(V100_common) and mean CTV coverage for all pairs of observer with common prescription volume of respective pairs(V100_pair) were also computed. RESULTS: The mean ±â€¯standard deviation(SD) of CI and COIN ranged from 0.756 ±â€¯0.076 to 0.840 ±â€¯0.070 and 0.591 ±â€¯0.090 to 0.673 ±â€¯0.06 respectively. When a plan made for CTV of individual observer was evaluated on CTV of all observers, the maximum variations(ρ < 0.05) in the mean CI,COIN,OI and EI were 10.6%,11.4%,10.6% and 72.7% respectively. The observed mean ±â€¯SD of V100, CIcommon of V100, CTV coverage with V100_common and V100_pair was 160.7 ±â€¯52.1, 0.70 ±â€¯0.09, 73.1 ±â€¯8.1% and 77.9 ±â€¯7.3% respectively. CONCLUSION: Inter-observer variation in delineation of CTV showed significant dosimetric impact with mean CTV coverage of 73.1% and 77.9% by common and paired prescription dose volume respectively among all observers.

Comparative assessment of late toxicity in patients of carcinoma cervix treated by radiotherapy versus chemo-radiotherapy - Minimum 5 years follow up.

BACKGROUND: A randomised trial was carried out comparing chemo-radiation (CTRT) vs. radiotherapy (RT) in patients of carcinoma cervix and showed similar rates of pelvic disease control, disease free survival and overall survival. Late toxicity is presented. METHODS: Between December 2000 and July 2006, 180 patients of carcinoma cervix were randomly assigned to RT + weekly cisplatin (n = 94) or RT alone (n = 86). Late toxicity was prospectively scored using RTOG criteria in 156 evaluable patients, 79 and 77 respectively and is presented as crude incidence for rectum, bladder, small intestine, vagina, skin and bone and also as actuarial incidence for rectum and bladder. RESULTS: The median follow up of surviving patients was 10.4 years (minimum - 6.5 years). Crude incidence, CTRT vs. RT, of late toxicities were: rectal (7.5% vs. 5%, p = 0.22), bladder (15% vs. 10.4%, p = 0.76), small bowel (3% vs. 1.2%, p = 0.51), vagina (25% vs. 35%, p = 0.35) while the actuarial risk of grades 3-5 rectal and bladder toxicities by 5 years were 13% vs. 10% (p = 0.698) and 16% vs. 14.8% (p = 0.783) respectively. Bladder toxicity appeared later then rectal toxicity (median 49.4 vs. 21.4 months). Severe bone toxicity (fractures) were higher in the CTRT arm, 5% vs. 0%, p = 0.018. On multivariate analysis vaginal involvement (p = 0.016) and bulky tumor (p = 0.020) were associated with severe vaginal morbidity while rectal point dose > 80% (p = 0.040) was associated with a higher incidence of rectal toxicity. CONCLUSION: Bone toxicity was significantly increased by addition of CT to RT and patients continued to experience toxicity at longer periods of follow up albeit disease free.

Change of target volume and its dosimetric impact during the course of accelerated partial breast irradiation using intraoperative multicatheter interstitial brachytherapy after open cavity surgery.

PURPOSE: To investigate the change of clinical target volume (CTV) and its dosimetric impact during the course of accelerated partial breast irradiation (APBI) using intraoperative multicatheter interstitial brachytherapy after open cavity surgery. METHODS AND MATERIALS: Twenty-two patients of APBI with intraoperative placement of catheters underwent computed tomography scans for the treatment planning before the first (CT1) and the last (CT2) treatment fraction. Delineation of lumpectomy cavity and CTV was done consistently on both CT data sets by one of the coauthors. Optimum plan (PCT1) was made on CT1. PCT1 was manually reproduced in CT2 which yielded plan PCT2. Plans were compared using coverage index (CI), dose homogeneity index (DHI), external volume index (EI), overdose volume index (OI) and conformal index (COIN). RESULTS: The mean ± SD volume of lumpectomy cavity and CTV was 78.5 ± 40.7 cm3, 156.4 ± 69.0 cm3 for PCT1, and 84.7 ± 50.1 cm3 (p = 0.11), 165.7 ± 82.8 cm3 (p = 0.15) for PCT2, respectively. CTV volume increase by ≥ 10% was observed in 9 cases however decrease of ≥10% was observed in 5 cases. Mean (SD) of absolute pairwise difference in CTV volume was found to be 13.2 (6.7) %. For cases with increase in CTV volume, significant (p < 0.05) decrease of 8.4%, 12.2%, and 5.5% was observed in CI, EI, and COIN of CTV respectively. However for cases with shrinkage of CTV, significant (p = 0.004) increase of 45% in EI was observed, whereas COIN reduced significantly (p = 0.001) by 13.5%. Overall 22 cases showed significant decrease of 5.8% and 8.1% in mean CI and COIN, respectively. CONCLUSIONS: The change of CTV during the course of APBI using intraoperative multicatheter interstitial brachytherapy after open cavity surgery was found patient specific and showed a significant impact on coverage and conformity.

Interobserver variations of target volume delineation and its impact on irradiated volume in accelerated partial breast irradiation with intraoperative interstitial breast implant.

PURPOSE: To investigate the interobserver variations in delineation of lumpectomy cavity (LC) and clinical target volume (CTV), and its impact on irradiated volume in accelerated partial breast irradiation using intraoperative multicatheter brachytherapy. MATERIAL AND METHODS: Delineation of LC and CTV was done by five radiation oncologists on planning computed tomography (CT) scans of 20 patients with intraoperative interstitial breast implant. Cavity visualization index (CVI), four-point index ranging from (0 = poor) to (3 = excellent) was created and assigned by observers for each patient. In total, 200 contours for all observers and 100 treatment plans were evaluated. Spatial concordance (conformity index, CIcommon, and CIgen), average shift in the center of mass (COM), and ratio of maximum and minimum volumes (Vmax/Vmin) of LC and CTV were quantified among all observers and statistically analyzed. Variation in active dwell positions (0.5 cm step) for each catheter, total reference air kerma (TRAK), volume enclosed by prescription isodose (V100%) among observers and its spatial concordance were analyzed. RESULTS: The mean ± SD CIcommon of LC and CTV was 0.54 ± 0.09, and 0.58 ± 0.08, respectively. Conformity index tends to increase, shift in COM and Vmax/Vmin decrease significantly (p < 0.05), as CVI increased. Out of total 309 catheters, 29.8% catheters had no change, 29.8% and 17.5% catheters had variations of 1 and 2 dwell positions (0.5 cm and 1 cm), respectively. 9.3% catheters shown variations ≥ 10 dwell positions (5 cm). The mean ± SD CIcommon of V100% was 0.75 ± 0.11. The mean observed Vmax/Vmin of prescription isodose and TRAK was 1.18 (range, 1.03 to 1.56) and 1.11 (range, 1.03 to 1.35), respectively. CONCLUSIONS: Interobserver variability in delineation of target volume was found to be significantly related to CVI. Smaller variability was observed with excellent visualization of LC. Interobserver variations showed dosimetric impact on irradiation of breast tissue volume with prescription dose.

A rare case of multicentric carcinoma left breast synchronous with carcinoma right lung: Therapeutic challenge in radiotherapy.

Multiple primary malignancies (MPMs) are a known phenomenon. We present a rare case of multicentric carcinoma of left breast synchronous with carcinoma of right lung. There was a diagnostic dilemma about the nature of the lung lesion, which otherwise would have been labeled as a metastasis from the breast primary; however, the immunohistochemistry markers distinguished between the two. The challenges in delivering radiotherapy in such not-so-conventional situations have been discussed. In spite of snag situation, patient can be treated safely with modern techniques and acceptable morbidities.

Breath-holding times in various phases of respiration and effect of respiratory training in lung cancer patients.

INTRODUCTION: Breath-holding (BH) technique is used for reducing the intrafraction-tumour motion in mobile lung tumours treated with radiotherapy (RT). There is paucity of literature evaluating differences in BH times in various phases of respiration in patients with lung cancer. METHODS: One hundred consecutive patients with lung cancer planned for radical RT/chemoradiation were accrued in the study. Eighty-seven patients were eligible for analysis at RT conclusion. Baseline pulmonary function test (PFT) were performed in all patients, and respiratory training was given from the day of RT planning. Deep inspiration breath hold (DIBH), deep expiration breath hold (DEBH) and mid-ventilation breath hold (MVBH) were recorded manually with a stopwatch for each patient at four time points (RT planning/baseline, RT starting, during RT and RT conclusion). RESULTS: Median DIBH times at RT planning, RT starting, during RT and RT conclusion were 21.2, 20.6, 20.1 and 21.1 s, respectively. The corresponding median DEBH and MVBH times were 16.3, 18.2, 18.3, 18.5 s and 19.9, 20.5, 21.3, 22.1 s, respectively. Respiratory training increased MVBH time at RT conclusion compared to baseline, which was statistically significant (19.9-22.1 s, P = 0.002). DIBH or DEBH times were stable at various time points with neither a significant improvement nor decline. Among various patient and tumour factors Forced Vital Capacity pre-bronchodilation (FVCpre ) was the only factor that consistently predicted DIBH, DEBH and MVBH at all four time points with P value <0.05. CONCLUSIONS: BH was well tolerated by most lung cancer patients with minimum median BH time of at least 16 s in any of the three phases of respiration. Respiratory training improved MVBH time while consistently maintaining DIBH and DEBH times throughout the course of radiotherapy.