TREATMENT OUTCOME AND TOXICITY OF HYPOFRACTIONATED RADIOTHERAPY WITH CONCOMITANT CHEMOTHERAPY VERSUS CONVENTIONAL FRACTIONATED CONCOMITANT CHEMORADIATION IN LOCALLY ADVANCED HEAD-AND-NECK CARCINOMA: A COMPARATIVE STUDY

Objectives: In our study, radiation of a higher dose per fraction (2.75 Gy/fraction, total dose of 55 Gy/20 fractions/4 weeks) with concomitant chemotherapy was compared with conventional chemoradiation (2 Gy/fraction, a total dose of 66 Gy/33 fractions/6 and half weeks, with concomitant chemotherapy), in patients of locally advanced squamous cell carcinomas of head and neck in terms of efficacy and toxicities. Methods: A total of 75 patients registered at the Department of Radiotherapy, NRS Medical College and Hospital, Kolkata, were allotted in two arms chronologically in a 1:1 ratio. Arm A – Patients received hypofractionated radiotherapy, 55 Gy/20 fractions in 4 weeks with concomitant weekly cisplatin (40 mg/m2). Arm B – Patients received conventional radiotherapy, 66 Gy/33 fractions in 6½ weeks with concomitant weekly cisplatin (40 mg/m2). Results: Both in terms of efficacy and toxicities, the hypofractionation arm was comparable to the conventional arm, and no statistically significant difference was present between the arms. For the study arm, complete response was 56.6%, partial response was 36.6%, and for control arm, complete response 50% and partial response 37.5% (p=0.750). In terms of acute toxicities and late dysphagia, both the arms were almost similar. Conclusion: The hypofractionated regimen was associated with tolerable acute and late toxicities and satisfactory local control. Considering the patient load, the overall treatment time, and the cost of hospital stay, this hypofractionated regimen is a good treatment option in our low-resource setup

Marjolin’s ulcer – epidemiology and the pattern of care: Experience from a tertiary cancer care center

Background: Marjolin’s ulcer (MU) reflects the malignant transformation of scar tissue or chronic inflammatory skin lesions. Due to the low incidence, only a few case reports and case series were reported in the literature to date. Aims and Objectives: In our retrospective analysis, we report our experience regarding MU over the past 16 years with a significant range of latent period, histology, and as well as underlying skin conditions, from Kolkata, India. Materials and Methods: This was a single institutional retrospective study carried out in the department of radiotherapy at the tertiary cancer, Kolkata. We focus mainly on data pertaining to the type of injury, the time gap between the initial injury and development of MU, histology, clinical stage, and treatment received, along with demographic details. Results: A total of 39 patients with histopathologically proved MUs were included according to the inclusion and exclusion criteria. The median age of patients at the time of development of MU was 52 years and with a range of 32–71 years. Out of 39 patients who participated in this study, 29 were male (74%) and ten were female (26%), 31 patients have localized disease (80%) and eight patients have metastatic disease (20%). The most common histology is squamous cell carcinoma and the least common histology was spindle cell sarcoma. The majority of the patients were treated with curative intention and a small proportion of patients were offered palliative therapy. Conclusion: Ulcers refractory to basic wound care, chronic in nature, and recent change of character of long-standing scar or wound, diagnosis of MU should be ruled out by biopsy. The management of MU should be supervised by a multidisciplinary tumor board and in the areas of epidemiology and treatment, more research is needed

Outcome of neoadjuvant chemotherapy followed by concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone in non-metastatic locally advanced non-small cell lung cancer – A prospective and randomized study

Background: Sequential chemoradiotherapy and concurrent chemoradiotherapy are two treatment options for locally advanced non-small cell lung cancer (NSCLC). Still there is limited data regarding which is the better treatment option. Aims and Objectives: This study is to compare the response rate and toxicity pattern between induction (neoadjuvant) chemotherapy followed by concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone in locally advanced NSCLC patients. Materials and Methods: A total of 48 Stage III NSCLC patients were selected for the study and were randomized into two arms with a 1:1 ratio. Patients of ARM-1 received concurrent chemoradiotherapy alone of a total dose of 66Gy/33# over 6 and ⅟2 weeks with paclitaxel (50 mg/m2) and carboplatin (Area under curve [AUC] 2) once every week. The study arm (ARM-2) received two cycles of induction chemotherapy with paclitaxel (175 mg/m2) and carboplatin (AUC 6) every 3 weeks and concurrent chemoradiotherapy (same CRT as on ARM-1). Results: In our study, overall response rate (Complete response+Partial response) in Arm 1 and Arm 2 was 62% and 71%, respectively. The treatment was very tolerated in our study. A mean follow-up of 12 months by Kaplan–Meier survival analysis showed a statistically non-significant difference in disease-free survival in both arms. Progression-free survival was numerically superior in the induction chemotherapy arm but the difference was statistically non-significant. Acute hematological toxicity was numerically more in the concurrent chemoradiotherapy arm, but statistically not significant. Acute lung toxicity, acute pharynx, and esophagus toxicity were numerically more in the induction chemotherapy arm but statistically non-significant. Conclusion: There was no significant difference between induction chemotherapy followed by concurrent chemoradiotherapy and concurrent chemoradiotherapy alone in the present study population

The bifurcation level and geometric anatomy of abdominal aorta – Does it matter in cervical malignancy? Experience from tertiary cancer center

Background: The course, the origin of the branch, and the division of the aorta may vary and the aortic bifurcation level and branching can be determined by arteriogram, magnetic resonance imaging, computed tomography (CT) scan, and cadaveric dissection. Aims and Objectives: This study aimed to find the variation in aortic bifurcation levels in cervical malignancy patients who underwent radiotherapy. Materials and Methods: Between January 2018 and December 2022 previously untreated, histologically proven squamous cell carcinoma of the cervix patients who received radiotherapy in our department were selected for this retrospective analysis. A planning contrast-enhanced CT scan with a 3 mm slice thickness was done in a CT simulator to delineate the target volume and aorta, common iliac vessels in all patients. Results: 407 cervical carcinoma patients who received radiotherapy in Linear Accelerator (LINAC) were included in this analysis. The aortic bifurcation is most commonly situated at the level of the L3–L4 intervertebral disc in 290 (71.25%) cases with a range between the upper L3 body and the lower L5 body. The common iliac bifurcation was situated at the level of L5–S1 in 338 cases (83.04%) and S1 vertebral body in 63 cases (15.47%). The average length of the left common iliac artery was 4.58 cm and the right common iliac artery was 4.44 cm. The diameter of the aorta at the level of just before the bifurcation is 1.39 cm. The average diameter of the left common iliac artery and right common iliac artery were 1.21 cm and 1.13 cm, respectively. The right and left take-off angles (αR, αL) are 25.58° and 23.78°, respectively. Conclusion: The knowledge regarding the anatomic variation of branching and bifurcation of the aorta of utmost importance for surgical procedures, interventional radiology procedures, and proper radiotherapy treatment planning. Acknowledging these anatomic variations may also reduce complications

Management of giant cell tumor of bone in the era of denosumab: A case series and review of the literature

Giant cell tumor (GCT) of the bone also known as osteoclastoma typically arises from the meta-epiphyseal region of the long bone and comprises 5% of all bone tumors and 20% of benign bone tumors. Understanding pathogenesis is the key to successful systemic therapy with denosumab, a RANK-ligand inhibitor. In this context, we report seven GCT bone-treated denosumab and radiotherapy cases with a diverse clinical presentation from our institute, NRS Medical College, and Hospital Kolkata

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Prevalence of serum sub-optimal Vitamin D3 levels and its correlation with treatment outcome, sociodemographic profile among cancer patients: A retrospective analysis.

Abstract Objectives: In areas of etiology and prevention of cancer research, vitamin D3 is currently one of the most promising agents. By virtue of anti-inflammatory, immunomodulatory, antiangiogenic, and proapoptotic effects, vitamin D3 may inhibit carcinogenesis, cancer cell proliferation, and tumor progression. we wanted to study the prevalence of vitamin D3 deficiency among cancer patients and whether there is any correlation between this vitamin D3 level with response to the treatment of cancer and survival. Methods: Between, January 2014 to December 2017, one ninety-nine patients, completed treatment at our radiotherapy department (N. R. S. Medical College and Hospital, Kolkata) included in the study. A venous blood sample, in a non-fasting state, was obtained during the follow-up period, and serum level of Vitamin D3 was determined by Chemiluminescence Immunoassay (CLIA) method. Results: A higher prevalence of suboptimal D3 concentration was seen in patients with stable or progressive disease than in those patients cured, this was statistically significant. The Complete response (CR) Vs partial response (PR) and progressive disease (PD) p- values are 0.0001 and 0.0008 respectively. Overall survival (OS) difference between D3 sufficiency and insufficiency is not statistically significant (p- 0.4422). But overall survival (OS) difference between D3 sufficiency and deficiency is statistically significant (p- 0.0001). Similarly, the overall survival (OS) difference between D3 insufficiency and deficiency is statistically significant (p- 0.0001) Conclusions: Vit. D3 level is significantly associated with response and there is also a positive correlation with overall survival (OS). Statistically significant (p- 0.0001) Overall survival (OS) difference between D3 insufficiency and deficiency is present. Statistically significant higher prevalence of suboptimal D3 concentration was seen in patients with stable or progressive disease than in those patients cured. Keywords: Vit. D3, deficiency, cancer, overall survival

TREATMENT OUTCOME AND TOXICITY OF NEOADJUVANT CHEMOTHERAPY FOLLOWED BY CONCOMITANT CHEMORADIOTHERAPY VERSUS CONCOMITANT CHEMORADIATION ALONE IN LOCALLY ADVANCED CERVICAL CARCINOMA: A COMPARATIVE STUDY

Objectives: This study intended to explore the outcome, and toxicities of neoadjuvant chemotherapy in addition to standard treatment concomitant chemoradiation in locally advanced cervix cancer. Methods: Sixty-two (n=62) locally advanced cervical carcinoma patients were randomized into two arms: The controlled arm (30 patients) received concomitant chemoradiation with external beam radiation therapy of 50 Gy to the whole pelvis and Inj. Cisplatin (40 mg/m2/week) alone and the study arm (32 patients) received three cycles, neoadjuvant chemotherapy with Inj. Paclitaxel (175 mg/m2), and Inj. Cisplatin (75 mg/m2) at 3 weekly intervals, followed by concomitant chemoradiation with external beam radiation therapy (EBRT) of 50 Gy to whole pelvis and Inj. Cisplatin (40 mg/m2/week). Responses to treatment, toxicities, disease-free survival, and progression-free survival (PFS) were analyzed in both arms. Results: Among the total of 62 patients, 30 were in the concomitant chemoradiation alone arm and 32 were in neoadjuvant chemotherapy followed by the concomitant chemoradiation arm. The median follow-up period was about 13 months. The tumor response in the form of complete or partial responses was equivalent in the two arms. The disease-free survival and the PFS were also comparable in both arms. The acute and the late toxicities were also comparable in the two arms. Conclusions: This study showed that neoadjuvant chemotherapy with paclitaxel and cisplatin before definitive concomitant cisplatin-based chemoradiation can be used as an alternative in the management of locally advanced carcinoma of the cervix

TOXICITY AND TREATMENT OUTCOME OF ACCELERATED FRACTIONATION RADIOTHERAPY VERSUS CONVENTIONAL FRACTIONATED CONCOMITANT CHEMORADIATION IN LOCALLY ADVANCED CERVICAL CARCINOMA: A PROSPECTIVE STUDY

Abstract Background and objectives: The benefit of concurrent chemoradiation is often not achievable because of poor tolerance due to increased toxicity, which is a common problem in our setting where a significant portion of carcinoma cervix patients presents at an elderly age, with medical co-morbidities, and with poor performance status. In addition, many patients refuse chemotherapy. Accelerated radiation therapy remains one of the possible alternatives there. Hence, we would like to perform a prospective study to compare treatment results between Pure Accelerated Radiation versus Concomitant Chemoradiation in Locally Advanced Squamous Cell Carcinoma of Cervix. Material and methods. After the initial investigative work up a total of Sixty-two (n=62) histologically confirmed squamous cell carcinoma of cervix Locally advanced Stage (FIGO- stage IB2 to IVA.) with ECOG performance status 0-2 patients were randomized into two arms: Arm A (Study arm, n=30 ) - Patients received&nbsp; 6 (Six) fractions per week of External Beam Radiotherapy without chemotherapy and Arm B (Control arm, n=32) patients received concurrent chemoradiation with 5 (Five) fractions per week of radiation with Weekly Injection of Cisplatin at the dose of 40 mg /m2. Results: Overall response rates between the two arms were similar and statistically not significant (p- value=0.352). All acute late toxicities are similar in both arms except acute renal toxicity which is more in the control arm and the difference is statistically significant (p-value =0.005) Conclusions: In developing countries like India with limited treatment facilities, pure accelerated radiotherapy with brachytherapy, without concurrent chemotherapy may be a good option and it can be viewed as an equally effective option for the elderly patients, the patients who refuse, those who have contraindications for chemotherapy or have comorbidities. Further multicenter, controlled, phase III trials will be needed to prove the benefit of the shortening overall treatment time and compare the efficacy with chemoradiation. Keywords: Accelerated fractionation, chemoradiation, cervical cancer

MEDULLARY CARCINOMA OF THE BREAST-EPIDEMIOLOGY, THE PATTERN OF CARE, AND TREATMENT OUTCOME: EXPERIENCE FROM THE TERTIARY CANCER CARE CENTER

Objectives: Medullary breast carcinoma is a very rare subtype of invasive ductal carcinoma breast which accounts for about 1–7% of all breast carcinoma. The natural history of this uncommon histological subtype is unknown because of the lack of adequate reported data in the literature and the rare variety of this tumor. In our retrospective analysis, we have tried to identify demographic clinicopathological features and treatment outcomes of this rare subtype. Methods: Between January 2012 and December 2017, total of 1271 breast carcinoma cases were identified, and clinic pathological, demographic profile, and treatment received were recorded from the medical records file. American joint committee on Cancer tumor, node, and metastasis system was used for staging. Results: Out of 1271 breast carcinomas, 19 histologically confirmed medullary carcinoma cases were identified and constitute about 1.5% of the total case. About 78% of patients were with Stage II and Stage III disease at the time of diagnosis. Eleven patients were initially treated with MRM followed by adjuvant chemotherapy and radiotherapy. Eight patients received neoadjuvant chemotherapy followed by surgery and radiotherapy. In addition to cytotoxic chemotherapy, two patients received trastuzumab also. None of the patients received hormone therapy as all the patients were hormone receptor-negative. Conclusions: Out of all invasive carcinoma, approximately 1.5% of cases were medullary carcinoma. About 90% of cases were triple-negative. Triple-negative breast cancer is usually associated with poor outcomes but medullary carcinoma despite being triple-negative, patients with medullary carcinoma have a good chance of long-term survival