Predictive and Prognostic Role of Tumor-Infiltrating Lymphocytes in Patients with Advanced Breast Cancer Treated with Primary Systemic Therapy.

INTRODUCTION: Tumor-infiltrating lymphocytes (TILs) are gaining recognition as an important immunological biomarker with therapeutic potential in breast cancer. In this cohort study conducted on patients with advanced breast cancer treated with primary systemic therapy (PST), the TILs concentration was correlated with response to PST and survival outcomes. METHODS: Patients with primary breast cancer treated with PST between 2016 and 2020 were included in this study, approved by IEC, and registered on ClinicalTrials.gov (NCT05250336). Tumor core biopsies obtained prior to starting treatment from 489 patients were assessed for the proportion of stromal TILs by standardized method and categorized into low (0-10% immune cells), intermediate (11-59%), and high (≥ 60%) TILs. TIL concentration and complete pathological response (pCR), disease-free survival (DFS), and overall survival (OS) were correlated. RESULTS: Of the 489 patients, 372 matched the eligibility criteria for assessment of TILs and made the final study cohort. Among these, 135 were luminal, 129 HER2-enriched, and 108 triple-negative breast cancers (TNBC). Proportions of patients with high TILs were greater in TNBC (15.7%) and HER2-enriched (9.3%), compared to luminal cancers (4.4%). High TIL concentration was correlated with higher pCR in all subtypes. A pCR was achieved in 33.3, 50, and 52.9% of high TIL patients in luminal, HER2-enriched, and TNBC subtypes, respectively (p < 0.05). High TILs were linked to longer DFS and OS in TNBC and HER2-enriched breast cancers. CONCLUSION: In this first study of its kind from a low- and middle-income country, high TILs concentration was found to be a predictor of response to PST across all breast cancer subtypes. TILs concentration was found predictive of better DFS and OS in TNBC and HER2-enriched cancers. Prognostic role of TILs in luminal cancers was not so apparent.

Cost Analysis on Total Cost Incurred (Including Out-of-pocket Expenditure and Social Cost) During Palliative Care in Cases of Head-and-Neck Cancer at a Government Regional Cancer Centre in North India.

Objectives: Palliative care involves providing symptomatic relief from the pain and stress of a severe illness to markedly improve the quality of life for both the patients and their families. It imposes high indirect costs on the patients. The study was conducted at SGPGIMS, which caters to 500 head-and-neck cancer patients annually. Out of these, 30-40% of cases require dedicated palliative care. Unfortunately, often, when patients reach the stage of palliative care, they have exhausted their all financial reserves. Therefore, a cost analysis of total cost incurred (including out-of-pocket expenditure and social cost) during palliative care in cases of head-and-neck cancer at a Government Regional Cancer Centre was undertaken. Material and Methods: The study is a descriptive study and the study sample consisted of (a) patients who had undergone surgery, chemotherapy, or radiotherapy and had recurred/relapsed and were now candidates for palliative care and (b) patients who presented de novo to the Regional Cancer Centre, SGPGIMS with advanced-stage disease, where the cure was not possible. The expenditure incurred was obtained retrospectively and prospectively from the study samples. Results: The out-of-pocket expenditure per patient per day was INR 2044.21. The social cost per patient per day was INR 518.21. Out of the total expenditure of INR 2562.42/patient/day, 80% of the cost was out-of-pocket expenditure and the remaining 20% was social cost borne by the patient. Conclusion: The study thus added to perspective on the average expenditure on out-of-pocket expenses and social costs being incurred as of date, while getting palliative care for head-and-neck cancer at a Regional Cancer Centre.

Post-chemotherapy target volumes are safe as boost volume for intact breast radiotherapy in locally advanced breast cancer.

PURPOSE: The purpose of our study is to evaluate the challenges in identification of postoperative complexes (POC), the utility of clips in delineation of clinical target volume for boost in LABC downstaged with neoadjuvant chemotherapy (NACT) and to correlate this with patterns of recurrence. METHODS AND MATERIALS: LABC patients who underwent NACT followed by BCS and radiotherapy (2007-2014) were the subject of our analysis. The data on visibility and characteristics of postoperative cavity (POC), concordance of its volume with clip volume on radiation planning scan were retrieved. A 1 cm margin beyond POC was delineated as a clinical target volume (CTV). Postoperative whole breast and supraclavicular radiotherapy (50 Gy/25fractions/5wk or 42.4 Gy/16#/3 wk) followed by boost (10-16 Gy/5-8#/1-1.5wk) were delivered. Patterns of recurrence were evaluated. RESULTS: Out of 60 patients, 28.3% patients had stage II disease and 71.7% had stage III disease. 25% patients achieved pathological CR (complete response). The median POC volume was 30 cc and the median clip volume was 40 cc. The concordance of POC volume with clip volume was seen in 80%. Clips served as a good surrogate for POC in 80% of patients. At a median follow-up of 65 months (IQ range 32-84 months), and a lost to follow-up rate of 11.6 %, 3.3% (n = 2) patients had local recurrence (LR) and 8.3% (n = 5) had regional recurrence (LRR) in the supraclavicular region. CONCLUSIONS: Delineation of post NACT excision cavity as POC for boost radiotherapy is safe. Clips serve as a good surrogate for CTV delineation in 75% patients.

Surgical Outcomes of Primary Versus Post-Neoadjuvant Chemotherapy Breast Conservation Surgery: A Comparative Study from a Developing Country.

INTRODUCTION: In India and other developing countries, breast conservation surgery (BCS) rates in breast cancer patients are low due to advanced disease at presentation and misconceptions about BCS outcomes. Many patients presenting with large or locally advanced breast cancers (LABC) can be offered post-neoadjuvant chemotherapy (NACT) BCS, safety of which is not as well established as that of primary BCS. This retrospective study compared pathological and surgical outcome parameters in patients undergoing primary and post-NACT BCS. METHODS: All non-metastatic breast cancer patients undergoing BCS during 2011-2015 with 1-year follow-up were included. Outcome parameters in form of margin infiltration, ipsilateral breast tumor recurrence (IBTR) rates and IBTR-free survival were compared between primary and post-NACT BCS patients groups. RESULTS: One hundred and twenty-nine patients underwent BCS; 95 underwent primary and 34 post-NACT BCS. Patients in both groups underwent similar multimodality treatment as per institutional protocols. Post-NACT patients more frequently required oncoplastic volume displacement or replacement surgery (p = 0.002). Re-excision of infiltrated margins was needed more frequently in primary BCS compared with post-NACT BCS group (14.4 vs. 8.8%; p = 0.40). IBTR (Mean follow-up = 30.7 months) was seen in 8.8% post-NACT patients compared with 2.1% primary BCS (p = 0.114). IBTR-free survival did not differ significantly between the groups in stage-wise comparison. CONCLUSION: Post-NACT BCS is safe even in large tumors and LABC, though many require oncoplastic procedures for satisfactory cosmesis. In a developing country where many patients present with large breast cancers or LABC, the benefits of BCS can be offered to a majority with the help of NACT, without compromising the chances of cure.

Generalized Multifactor Dimensionality Reduction (GMDR) Analysis of Drug-Metabolizing Enzyme-Encoding Gene Polymorphisms may Predict Treatment Outcomes in Indian Breast Cancer Patients.

BACKGROUND: Prediction of response and toxicity of chemotherapy can help personalize the treatment and choose effective yet non-toxic treatment regimen for a breast cancer patient. Interplay of variations in various drug-metabolizing enzyme (DME)-encoding genes results in variable response and toxicity of chemotherapeutic drugs. Generalized multi-analytical (GMDR) approach was used to determine the influence of the combination of variants of genes encoding phase 0 (SLC22A16); phase I (CYP450, NQO1); phase II (GSTs, MTHFR, UGT2B15); and phase III (ABCB1) DMEs along with confounding factors on the response and toxicity of chemotherapeutic drugs in breast cancer patients. METHODS: In an Indian breast cancer patient cohort (n = 234), response to neo-adjuvant chemotherapy (n = 111) and grade 2-4 toxicity to chemotherapy were recorded. Patients were genotyped for 19 polymorphisms selected in four phases of DMEs by PCR or PCR-RFLP or Taqman allelic discrimination assay. Binary logistic regression and GMDR analysis was performed. Bonferroni test for multiple comparisons was applied, and p value was considered to be significant at <0.025. RESULTS: For ABCB1 1236C>T polymorphism, CT genotype was found to be significantly associated with response to NACT in uni-variate and multi-variate analysis (p = 0.018; p = 0.013). The TT genotype of NQO1 609C>T had a significant association with (absence of) grade 2-4 toxicity in uni-variate analysis (p = 0.021), but a non-significant correlation in multi-variate analysis. In GMDR analysis, interaction of CYP3A5*3, NQO1 609C>T, and ABCB1 1236C>T polymorphisms yielded the highest testing accuracy for response to NACT (CVT = 0.62). However, for grade 2-4 toxicity, CYP2C19*2 and ABCB1 3435C>T polymorphisms yielded the best interaction model (CVT = 0.57). CONCLUSION: This pharmacogenetic study suggests a role of higher order gene-gene interaction of DME-encoding genes, along with confounding factors, in determination of treatment outcomes and toxicity in breast cancer patients. This can be used as a potential objective tool for individualizing breast cancer chemotherapy with high efficacy and low toxicity.

A Comparative Validation of Primary Surgical Versus Post-neo-adjuvant Chemotherapy Sentinel Lymph Node Biopsy for Stage III Breast Cancers.

INTRODUCTION: Sentinel lymph node biopsy (SLNB) is the standard of care for staging N0 primary early breast cancers (EBC). Patients in developing countries mostly present with large (LOBC) or locally advanced cancers (LABC) and are treated with neo-adjuvant chemotherapy (NACT). Accuracy of SLNB in staging stage III N0 and post-NACT N0 patients is uncertain. This prospective validation study on LOBC/LABC patients compared the accuracy of SLNB between primary versus post-NACT surgery. MATERIALS AND METHODS: Fifty T3/T4, N0 patients undergoing primary surgery (Group I) and 70 LOBC/LABC (index stage) treated with NACT and N0 at the time of surgery (Group II) were inducted. Validation SLNB was performed using low-cost methylene-blue and (99m)Tc-Antimony colloid. SLN identification (IR) and false-negative (FNR) rates were compared between the groups. Sub-group analysis was done in Group II per index tumor and nodal stage to identify factors predicting SLN IR and FNR in post-NACT patients. SLN IR and FNR in both groups were compared with those in previously published SLN validation study and meta-analysis in EBC. RESULTS: Using combination of blue-dye and radio-colloid, post-NACT SLN IR and FNR (82.9, 13.5 %) were far inferior to T3/T4 primary surgery group (94, 7.7 %; p values 0.034, 0.041) and in EBC. SLN IR using blue-dye alone was dismally low in post-NACT LABCs. Factors predicting unidentified post-NACT SLN and false-negative SLNB included young age, LVI, skin infiltration, extra-nodal spread or N2a stage, and UOQ tumors. CONCLUSIONS: Accuracy of SLNB in T3, N0 tumors undergoing primary surgery is comparable to that of SLNB for N0 EBC. In post-NACT patients, SLNB IR are lower and FNR are higher. Factors predictive of non-identification and false-negative SLNB include pre-NACT skin involvement (T4b), N2a stage or extra-nodal invasion and LVI, and to a lesser extent, young age and UOQ location of the tumor.

Outcomes of Triple-Negative Breast Cancers (TNBC) Compared with Non-TNBC: Does the Survival Vary for All Stages?

BACKGROUND: Triple-negative breast cancer (TNBC) is associated with aggressive tumor behavior and worse outcomes. In a study at a tertiary care breast unit in a developing country, clinico-pathological attributes and outcomes of patients with TNBC were compared with (c.w.) ER, PR, and/or HER2 expressing tumors (non-TNBC). PATIENTS AND METHODS: Medical records of 1213 consecutive breast cancer patients managed during 2004-2010 were reviewed. An evaluable cohort of 705 patients with complete treatment and follow-up (median 36 months) information was thus identified. Patients were categorized per ER, PR & HER2 status into TNBC, and ER/PR+ and/or HER2+ groups. Clinico-pathological parameters, response to NACT, and OS & DFS were compared between TNBC and non-TNBC groups. RESULTS: TNBC patients (n = 249) comprised 35.3 % of the study cohort (n = 705), and were significantly younger than non-TNBC patients (mean age 49.1 ± 11.2y c.w. 51.8 ± 11.3, p = 0.02). The TNM stage at presentation was similar in the two groups (Stage I and II-37 % c.w. 44.3 %, Stage III-47.5 % c.w. 39.5 %, Stage IV-15.5 % c.w. 16.2 % in TNBC c.w. Non-TNBC; p = 0.09). Tumor size (5.7 ± 2.9 cm TNBC c.w. 5.4 ± 2.8 cm non-TNBC, p = 0.22) was similar but lymph nodal (cN) metastases were more frequent in TNBC (77.3 % c.w. 69.8 %; p = 0.03). TNBC had higher histologic grade (97.1 % gr II/III in TNBC c.w. 91.2 % non-TNBC, p = 0.01) and higher incidence of LVI (20.4 % in TNBC c.w. 13.5 %, p = 0.03). Patient groups received similar multi-disciplinary surgical, radiation, and systemic treatment. Comparable proportion of patients in 2 groups were treated with NACT (42 % c.w. 38 %), which resulted in pathological complete response (pCR) in 27.5 % TNBC patients c.w. 17.1 % non-TNBC patients (p = 0.04). Both OS (81.8 ± 4.52 c.w. 97.90 ± 3.87 months, p < 0.001) and DFS (89.2 ± 5.1 c.w. 113.8 ± 4.3 months, p < 0.001) were shorter in TNBC than non-TNBC group. On stage-wise comparison, OS differed significantly only in stage III (47.4 ± 5.3 months in TNBC c.w. 74.5 ± 4.4 in non-TNBC; p < 0.001). Univariate and multivariate analyses revealed tumor stage and IHC subtyping into TNBC c.w. non-TNBC as most important factors predictive of survival. CONCLUSIONS: TNBC occurred at younger age and exhibited aggressive pathology as compared to non-TNBC patients. Although patients with TNBC exhibited better chemo-sensitivity, they had worse DFS and OS compared to the non-TNBC patients. The survival of Stage III TNBC patients was significantly worse compared to non-TNBC group; while in stages I, II, and IV, survival were not significantly different.

Initial Experience of Head and Neck Cancer Patients Treated in an Oncologist Led Palliative Cancer Care Clinic at a Tertiary Cancer Care Center in Uttar Pradesh: Is the Initiative of a Full-fledged Palliative Care for Cancer Patients Justified.

INTRODUCTION: Poor socioeconomic status and illiteracy attribute to the advanced presentation of head and neck cancer (HNC) patients in India and are candidates for palliation in our setup. We set up a palliative cancer care clinic (PCCC), and an audit of initial 153 HNC patients is presented. AIMS AND OBJECTIVES: To assess the impact of palliative cancer care services. METHODOLOGY: Data of advanced HNC patients suited for palliation were collected to document demography, symptomatology, cancer treatment, and supportive care. RESULTS: One hundred and fifty-three patients were seen during January 2013 to March 2015 in the PCCC. Seventy-two (47%) referral cases were due to disease progression and 81 (53%) due to de novo advanced cases. Median follow-up for this group was 5.3 months. Ninety (59%) cases needed some degree of assistance for their normal activities. Sixty-seven (44%) patients belonged to poor socioeconomic status and 65 (43%) were educated up to equivalent of high school. One hundred and thirty-five (88%) patients had an adequate family support. Pain was the most common presenting symptom in 134 (87%) cases with adequate relief in 112 (84%) patients with another 13 (09%) could not be assessed. Overall median duration of symptoms was 6 months. Cancer-directed therapy was used in 143 (93%) patients. Near the end of life in 47 (73%) out of 63 documented cases, caregivers were psychologically prepared for the inevitable. CONCLUSION: The role of palliative care team in alleviating physical, psychosocial, and emotional issues of patient and family members was significant. PCCC seems to be a feasible working model in our setup.

Comparison of set-up errors by breast size on wing board by portal imaging.

AIM: To quantify and compare setup errors between small and large breast patients undergoing intact breast radiotherapy. METHODS: 20 patients were inducted. 10 small/moderate size breast in arm I and 10 large breast in arm II. Two orthogonal and one lateral tangent portal images (PIs) were obtained and analyzed for systematic (Σ) and random (σ) errors. Effect of no action level (NAL) was also evaluated retrospectively. RESULTS: 142 PIs were analyzed. Σ(mm) was 3.2 versus 6.7 (p = 0.41) in the mediolateral (ML) direction, 2.1 versus 2.9 (p = 0.06) in the craniocaudal (CC) and 2.2 versus 3.6 (p = 0.08) in the anteroposterior (AP) direction in small and large breast, respectively. σ(mm) was 3.0, 3.3 and 3.3 for small breast and 4.1, 3.7 and 3.2 for large breast in the ML, CC and AP direction (p = 0.07, 0.86, 0.37), respectively. 3 D Σ(mm) was 2.7 versus 4.2 (p = 0.01) and σ(mm) was 2.5 versus 3.2 (p = 0.14) in arm I and II, respectively. The standard deviation (SD) of variations (mm) in breast contour depicted by central lung distance (CLD) was 5.9 versus 7.4 (p < 0.001), central flash distance (CFD) 6.6 versus 10.5 (p = 0.002), inferior central margin (ICM) 4 versus 4.9 (p < 0.001) in arm I and II, respectively. NAL showed a significant reduction of systematic error in large breast in the mediolateral direction only. CONCLUSION: Wing board can be used in a busy radiotherapy department for setting up breast patients with a margin of 1.1 cm, 0.76 cm and 0.71 cm for small breasts and 1.96 cm, 1.12 cm and 0.98 cm for large breast in the ML, AP and CC directions, respectively. The large PTV margin in the mediolateral direction in large breast can be reduced using NAL. Further research is needed to optimize positioning of large breasted women.

Relationship of MTHFR and NQO1 Pharmacogenetics and Chemotherapy Clinical Outcomes in Breast Cancer Patients.

The study aimed at evaluating the influence of MTHFR 677C>T and NQO1 609C>T polymorphisms in toxicity and response to chemotherapy in breast cancer patients. These two genes are involved in the folate homeostasis and bioactivation of chemotherapeutic drugs, respectively. In this study, 243 patients treated with FEC/FAC/methotrexate chemotherapy regimen were recruited and followed up for toxicity (NCI-CTCAE ver. 3). While out of 243 patients, 115 patients who received neo-adjuvant chemotherapy (NACT) were followed for treatment response. Genetic analysis of MTHFR 677C>T and NQO1 609C>T was done by PCR-restriction fragment length polymorphism. We found significant association of variant genotype (TT) of NQO1 609C>T with grade 2-4 toxicity [OR 0.33 (0.13-0.88), P = 0.027] and with grade 2-4 anemia [OR 0.34 (0.12-0.95), P = 0.041]. However, no association of MTHFR 677C>T was seen with either response to NACT or drug-induced toxicity. The study provides useful information for prediction of clinical outcomes in breast cancer patients in terms of NQO1 609C>T by evaluating its association with chemotherapy-induced toxicity.

Neuroblastic tumours in children: Outcome from a referral centre in India.

Background: There is a paucity of uniform literature on the outcome of children with neuroblastic tumours from developing countries. This study aims to present the outcome in children having neuroblastic tumours. Materials and Methods: We retrospectively reviewed patients with neuroblastic tumours from January 2014 to March 2020. Data analysed were pertaining to the age, sex, presentation, site, stage, diagnostic evaluation performed, management and follow-up results, etc., The final outcomes were assessed as complete response; partial response (PR); no response (NR) and progressive disease. International Neuroblastoma Risk Group staging was used and patients were categorised on the basis of age, site and stage of tumour. Overall survival (OS) was calculated from the date of diagnosis to the date of last follow-up and event for OS was death. Results: Forty-seven patients were included with median age of 60 months (ranges of 2-180; mean = 61.87 ± 47.56). About 72.3% (n = 34) patients were males. Out of total, 6.4% (n = 3), 53.2% (n = 25) and 38.3% (n = 18) were in stage L1, L2 and M, respectively, whereas 2.1% (n = 1) patients were in stage MS. Surgery was performed in 25 (53.19%) patients, but gross total excision was achieved in 48.90% (n = 23) patients. Onlu 10.60% (n = 5) patients were referred, whereas 14.89% (n = 7) patients reported recurrences. Mean and median follow-up time of the patients was 24.64 ± 16.04 and 18 months (range: 3-60 months). Out of total, 53.2% (n = 25) and 29.8% (n = 14) patients had complete and PRs, respectively, whereas 17% (n = 8) patients had NR. Out of the total 47 patients, 8 (17%) achieved events (deaths), whereas the rest, 39 (83%) patients, were censored. Mean event-free OS time was 50.04 months. Conclusion: There was a significant difference in patient deaths in recurrence and non-recurred patients (4/7, 57.1% vs. 4/40/, 10%, P = 0.011). Survival time was significantly higher in patients with stages L1-L2 as compared to Stage 4. Stage and age were found predictors of survival.

A comparative study of gemcitabine and cisplatin versus oral capecitabine alone in metastatic gallbladder cancer.

Aims: There is no consensus for palliative chemotherapy regimen in metastatic gallbladder cancer. We did a retrospective study to compare the treatment outcome in patients of metastatic gallbladder cancer treated with either gemcitabine + cisplatin (regimen A) or oral capecitabine (regimen B) alone. Subjects and Methods: A total of 67 patients between January 2015 and September 15 treated with either regimen A or regimen B were retrospectively evaluated. Statistical analysis was done in June 2019. Kaplan-Meir and Log rank test were used to compare survival between two arms. Results: Out of 67 patients, 31/67 (46%) received regimen A, and 36/67 (54%) received regimen B. Male to female ratio was 1:3. About 42% patients in regimen A and 20% in regimen B required palliative stenting. Median number of chemotherapy cycles was 4 in both regimen A (range 1->6) and regimen B (range 1->6). Patients receiving 3 cycles and 6 cycles of chemotherapy in regimen A and regimen B was 68% and 31% versus 70% and 63%, respectively (P = 0.86). Response assessment as any response (complete response + partial response + disease was stable) after 3 cycles and 6 cycles was 71% and 57% (P = 0.20), 44% and 39% (P = 0.29), in regimen A and B, respectively. Median survival was 23 weeks (range 2-106 weeks) in regimen A and 15 weeks (range 4-83 weeks) in regimen B (P = 0.40). Conclusions: The present study shows gemcitabine and cisplatin has nonsignificant better survival compared to oral capecitabine. However, oral capecitabine is more convenient and easy to administer. Studies with larger sample size are needed to further establish the standard chemotherapy guidelines.

Evaluation of Toll-like receptors 3 (c.1377C/T) and 9 (G2848A) gene polymorphisms in cervical cancer susceptibility.

Cervical cancer is emerging as a leading cause of morbidity and mortality in women worldwide. Toll-like Receptor (TLR) gene polymorphisms may contribute to subsequent inter-individual variability in cancer susceptibility. The present study aimed to identify the role of TLR 3 (c.1377C/T) [rs3775290] and TLR 9 (G2848A) [rs352140] gene polymorphisms in the risk of developing cervical cancer in North India. Peripheral blood samples were collected from 200 histopathologically confirmed cervical cancer patients from North India and 200 unrelated, cancer-free, age-matched healthy female controls of similar ethnicity. Genomic DNA was extracted using the salting-out method, and genotyped for TLR 3 and TLR 9 using polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP). Our data demonstrated a lack of association between TLR 3 (c.1377C/T) and TLR 9 (G2848A) gene polymorphisms and the risk of developing cervical cancer. TLR 3 CT + TT was marginally associated (P = 0.061; age-adjusted OR = 1.46; 95% CI = 0.98-2.16) with cervical cancer susceptibility. The AA genotype of TLR 9 showed borderline significance (P = 0.053) conferring a marginal increased risk (OR = 2.63, 95%CI = 0.99-7.01) for advanced cancer stages (III + IV). Further, TLR 3 and 9 polymorphisms did not have a significant role in modulation of risk due to tobacco usage in cervical cancer patients. Our study suggests only marginal role of TLR 3 and 9 gene polymorphisms in cervical cancer susceptibility in North India; however, future studies in ethnically diverse populations may provide a more comprehensive involvement of innate immunity in cervical cancer etiology in women worldwide.

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.

Fungating Breast Cancer: Experience in Low and Middle Income Country.

Fungating breast cancer (FBC) is a rare entity in developed nations. But this occurrence is not uncommon in our country. The aim of this study was to review clinico-pathologic profile and outcomes of FBC in a developing country. This retrospective study consisted of patients with FBC managed at our institute (Jan 2005-Dec 2015). Clinico-pathologic profile, management details, and outcomes were analyzed. The Kaplan-Meier method was used to determine overall survival (OS). Log-rank test was performed to compare survival in various subgroups. Seventy-nine patients were detected to have FBC constituting 3.3% of all breast cancers and 24.8% of those having T4b lesions. Mean age of the patients was 55 + 11 years. Ninety-six percent were women and 67% belonged to rural areas. A total of 75% women were postmenopausal. Mean duration of lump was 16 + 11 months. The mean tumor size was 8+ 2 cm. Eighty-seven percent had axillary lymph node involvement and 42% distant metastases. Fifty-eight percent (n = 46) patients had stage III and 42% (n = 33) stage had IV tumors. Hormone receptor (HR) positivity was noted in 44% (n = 35) and HER2/neu overexpression in 39% (n = 31) tumors, whereas 32% (n = 25) were triple negative. Overall, 95% (n = 75) of patients received chemotherapy, 91% (n = 72) patients underwent mastectomy, and 76% (n = 60) loco-regional radiotherapy. Median duration of follow-up was 40 (2-93) months. Median survival was 36 months, and 5-year OS was 40%. Except for stage (53% vs 22%, p = 0.005), no other factor influenced OS. Multimodality therapy in FBS results in good symptom palliation and comparable survival to stage III and IV patients without fungating tumors.

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.

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.

Objective and subjective assessment of xerostomia in patients of locally advanced head-and-neck cancers treated by intensity-modulated radiotherapy.

BACKGROUND: Parotid-sparing intensity-modulated radiotherapy (IMRT) effectively reduces xerostomia in head-and-neck cancer (HNC). Changes in the salivary output at 1 year were studied and correlation with quality of life (QOL) changes in patients of locally advanced HNC (LAHNC) was drawn. MATERIALS AND METHODS: Between October 2009 and October 2011, 20 patients of LAHNC were treated with IMRT using simultaneous integrated boost technique. High-risk clinical target volume (CTV) was given a dose of 66 Gy/30 fr, intermediate-risk CTV 60 Gy/30 fr, and low-risk CTV 54 Gy/30 fr. The saliva flow rate was estimated for 5 min at rest (unstimulated) and after using lemon drops (stimulated) for the next 5 min, at baseline (pretreatment), and 3, 6, and 12 months following treatment. Evaluation of patients' perception of dry mouth was done using EORTC-QLQ-C30 and HN35 questionnaires at the same time points. RESULTS: Baseline unstimulated and stimulated salivary flow rates were 0.659 ml/min and 1.69 ml/min, respectively. At 3 months, a significant reduction in unstimulated (0.346 ml/min) and stimulated (0.80 ml/min) flow rate was observed. Unstimulated flow rate continued to decrease further till 6 months (0.295 ml/min), but slight improvement was seen in stimulated flow rate (0.91 ml/min). At 12 months, minimal recovery was observed in both unstimulated (0.362 ml/min) and stimulated flow rates (1.09 ml/min). EORTC-QOL questionnaire mean scores for dryness and stickiness of saliva were 10 and 15 at baseline and increased to 36 and 25, respectively, at 3 months. At 6 months, symptom score for dryness further increased to 45 and then decreased to 33 at 12 months. Stickiness score remained static from 3 to 12 months. Salivary flow rate correlated well with dry mouth (P < 0.05) but not with the perception of sticky saliva (P = 0.82) at 6 months and beyond. CONCLUSIONS: Both salivary flow rate and xerostomia-related questions worsened at 3 months even with IMRT and showed a similar pattern of recovery.

Clinico-Pathological Profile of Anaplastic Thyroid Carcinoma in an Endemic Goiter Area.

INTRODUCTION: Anaplastic thyroid cancers (ATCs) usually present in the sixth to seventh decades of life and little is known about the disease in young patients. The aim was to analyze the clinicopathological characteristics diagnosed with ATC in an iodine-deficient area. MATERIAL AND METHODS: The medical records of 100 patients diagnosed with ATC at a tertiary care hospital between 1991 and 2013 were reviewed. RESULTS: The mean age of patient was 58 years. About 34 patients were ≤50 years. The common presentation was that of a rapidly growing fixed and hard mass (64%). Due to rapid expansion, 27% patients experienced severe pain. About one-third presented as sudden enlargement of pre-existing goiter over few weeks. The median duration of symptoms before diagnosis was 3 months. About 41% presented with lymph node enlargement and 31% with distant metastasis. The diagnosis was established with fine-needle aspiration or core biopsy. Histopathology was available in 32 patients and showed four major patterns: spindle cell (9), giant cell (7), epithelioid (5), squamoid (1), mixed type in 10 patients. Eight patients presenting with stridor required emergency tracheostomy for airway control. Total thyroidectomy with or without lymph node dissection was possible in 21 patients. Patients received radiotherapy with or without chemotherapy. Median overall survival was 3 months. Overall survival was significantly better in patients receiving some form of treatment. CONCLUSION: ATC in endemic goiter areas presents at an earlier age. One-third of ATC is due to anaplastic transformation of pre-existing goiter and majority of the patients refuse treatment due to dismal outcome.

Role of GSTM3 polymorphism in the risk of developing esophageal cancer.

GSTM3 is involved in detoxification of carcinogens and may be important in modulating cancer susceptibility. GSTM3 genotype frequencies were determined in peripheral blood DNA of 149 esophageal cancer patients and 200 nonmalignant controls using the PCR followed by PAGE. Patients who were heterozygous carriers of GSTM3 AB genotype had an enhanced risk for developing esophageal cancer [odds ratio (OR), 2.1; 95% confidence interval (95% CI), 1.1-3.7; P = 0.01]. In males, the risk due to GSTM3 AB genotype increased further (OR, 3.4; 95% CI, 1.7-6.8; P = 0.000). Interaction of GSTM3 AB + BB and GSTM1 null genotypes marginally modulated risk (OR, 2.3; 95% CI, 1.1-3.7; P = 0.01). Association with histology (adenocarcinoma: OR, 3.4; 95% CI, 1.1-10.9; P = 0.03) and tumor site (middle third location: OR, 2.2; 95% CI, 1.1-4.4; P = 0.01; lower third location: OR, 2.6; 95% CI, 1.2-5.6; P = 0.01) was also documented. Our results suggest that GSTM3 polymorphism may influence esophageal cancer susceptibility, in particular modulating the risk for adenocarcinoma histology and tumors of the mid and lower third region.