Indian Journal of Cancer

Shared decision making and cancer screening Filipe Prazeres, Elisa Martins Indian Journal of Cancer 2019 56(3):195-196

WT1 in astrocytomas: Comprehensive evaluation of immunohistochemical expression and its potential utility in different histological grades Aakriti Manocha, Sunila Jain Indian Journal of Cancer 2019 56(3):197-201 BACKGROUND: Wilms' tumor 1 (WT1) mutation has recently been detected in gliomas. Growing data indicate that WT1 mutation plays a causal role in gliomagenesis and is overexpressed in most glioblastomas. An emerging immunotherapy targeting WT1 has shown to be effective in resistant glioblastomas in clinical trials. WT1 expression and its potential utility in various grades of astrocytomas is still unclear and needs further elucidation. The evaluation of WT1 can be done by molecular or immunohistochemical methods. As immunohistochemistry is easier with wider routine use, immunoexpression of this biomarker was studied. AIM: The aim of this study was to characterize WT1 immunoexpression across different histological grades of astrocytomas to routinely aid in diagnosis and reproducibility and to assess the association between WT1 and immunomarker isocitrate dehydrogenase (IDH1). MATERIAL AND METHODS: This was an observational prospective study on 79 cases of astrocytomas. RESULTS: Seventy-nine astrocytomas including 11 recurrent tumors were assessed for WT1 by immunohistochemistry. WT1 expression was detected in all astrocytomas (100%). The control group of reactive gliosis was negative. WT1 score correlated with histological tumor grades (P < 0.001) with higher score in higher grade. It was also observed that different tumor grades depicted two distinct expression patterns. WT1 score and pattern were valuable in differentiating high- and low-grade astrocytomas. CONCLUSION: This study supports the oncogenic role of WT1 in astrocytomas. WT1 was found to be valuable in distinguishing different grades of astrocytomas. WT1 can aid in differentiating neoplastic process from reactive gliosis, particularly in recurrent tumors. Higher expression in glioblastomas supports its immunotherapy potential.

Evaluatıon of hypofractıonated stereotactıc radıotherapy (HFSRT) to the resectıon cavıty after surgıcal resectıon of braın metastases: A sıngle center experıence Ferrat Dincoglan, Omer Sager, Bora Uysal, Selcuk Demiral, Hakan Gamsiz, Esin Gündem, Yelda Elcim, Bahar Dirican, Murat Beyzadeoglu Indian Journal of Cancer 2019 56(3):202-206 INTRODUCTON: Adjuvant radiotherapy after surgical resection is used for the treatment of patients with brain metastasis. In this study, we assessed the use of adjuvant hypofractionated stereotactic radiotherapy (HFSRT) to the resection cavity for the management of patients with brain metastasis. MATERIALS AND METHODS: A total of 28 patients undergoing surgical resection for their brain metastasis were treated using HFSRT to the resection cavity. A total HFSRT dose of 25–30 Gray (Gy) was delivered in 5 consecutive daily fractions. Patients were retrospectively assessed for toxicity, local control, and survival outcomes. Kaplan-Meier method and log-rank test were used for statistical analysis. RESULTS: Median planning target volume (PTV) was 27.2 cc (range: 6–76.1 cc). At a median follow-up time of 11 months (range: 2–21 months.), 1-year local control rate was 85.7%, and 1-year distant failure rate was 57.1% (16 patients). Median overall survival was 15 months from HFSRT. Higher recursive partitioning analysis class (P = 0.01) and the presence of extracranial metastases (P = 0.02) were associated with decreased overall survival on statistical analysis. There was no radiation necrosis observed during follow-up. CONCLUSION: HFSRT to the resection cavity offers a safe and effective adjuvant treatment for patients undergoing surgical resection of brain metastasis. With comparable local control rates, HFSRT may serve as a viable alternative to whole brain irradiation.

Pazopanib efficacy and toxicity in a metastatic sarcoma cohort: Are Indian patients different? Aparna Sharma, Ilavarasi Vanidassane, Aditi Aggarwal, Asit Ranjan Mridha, Rambha Pandey, Ekta Dhamija, Adarsh Barwad, Sameer Rastogi Indian Journal of Cancer 2019 56(3):207-210 PURPOSE: There is no study till date determining the spectrum of adverse events of pazopanib in Indian patients with advanced sarcoma. MATERIALS AND METHODS: We conducted a retrospective study by analyzing the case records of metastatic sarcoma patients treated with pazopanib from January 2016 to July 2017 in sarcoma medical oncology clinic. Toxicity was assessed according to CTCAE v.4.03 criteria. SPSS version 23 was used for statistical evaluation. RESULTS: A total of 33 patients received pazopanib. The median age was 41 years (range, 19–75 years), with a male predominance (54.5%). Twenty-six patients (78.8%) had ECOG performance status 1 at the time of pazopanib initiation. The most common type of sarcoma was synovial sarcoma, and the mean duration of pazopanib intake in patients was 4.12 months. The median follow-up was 13 months. Median progression-free survival was 5 months, and median overall survival was 18 months. Overall response rate was 6.0%. Out of the 33 patients, 42.4% (n = 14) received it after first line of therapy. Six patients (18.2%) required dose reductions due to toxicity. Thirteen (39.4%) patients experienced CTCAE grade 3 or 4 toxicities. Most common grade 3 and 4 toxicities experienced among patients were hand–foot skin reaction (18.2%) and proteinuria (9.1%). No significant difference was seen when analyzed for variables such as age, sex, ECOG performance status, comorbidities, and number of previous lines received in patients experiencing grade 3 and 4 toxicities. CONCLUSIONS: The spectrum of adverse events in Indian patients at doses lower than the recommended dose is distinctly different from the western population. However, this unique toxicity profile needs to be validated in prospective studies.

A prospective, randomized study to compare the combination of imatinib and cytarabine versus imatinib alone in newly diagnosed patients with chronic phase chronic myeloid leukemia Priyanka Samal, Prantar Chakrabarti, Uttam K Nath Indian Journal of Cancer 2019 56(3):211-215 INTRODUCTION: To compare the efficacy and safety of imatinib and cytarabine (ara-c) combination versus imatinib monotherapy in newly diagnosed patients with chronic phase chronic myeloid leukemia (CML-CP). MATERIALS AND METHODS: This prospective, randomized study included adult patients (age >18 years) with newly diagnosed CML-CP. Patients received either a single oral dose of imatinib 400 mg/day in combination with a subcutaneous injection of ara-c 20 mg/m2/day (imatinib + ara-c) or a single oral dose of imatinib 400 mg/day. Primary endpoints were hematological and molecular responses at 3 months and cytogenetic responses at 6 and 12 months. Secondary endpoints included grade 3/4 hematological and nonhematological adverse events (AEs). RESULTS: Of 30 patients included, 14 were randomized to imatinib + ara-c and 16 to imatinib alone. Complete hematologic response (CHR) at 3 months was higher with imatinib + ara-c vs. imatinib alone (100% vs. 87.5%, P = 0.48). The median time to achieve CHR was significantly (P < 0.001) lower with imatinib + ara-c (32.07 vs. 23.43 days). Molecular response at 3 months was significantly higher (P = 0.04) with imatinib + ara-c vs. imatinib alone (100% vs. 68.75%). Complete cytogenetic response was also higher with imatinib + ara-c vs. imatinib alone (42.85% vs. 25% at 6 months and 71.4% vs. 62.5% at 12 months). Neutropenia followed by thrombocytopenia and anemia were the most common AEs. Grade 3/4 hematological and nausea events were significantly (P < 0.05) higher with imatinib + ara-c. Other nonhematological events were not significantly different between the treatments. The median follow-up duration was 20 months (range: 15–23 months). CONCLUSION: Imatinib with low-dose ara-c can be considered as a potential first-line treatment option for CML-CP.

Role of serum HE4 as a prognostic marker in carcinoma of the ovary Manikandan Lakshmanan, Vijay Kumar, Arun Chaturvedi, Sanjeev Misra, Sameer Gupta, Naseem Akhtar, Shiv Rajan, Kavitha Jain, Sudeep Garg Indian Journal of Cancer 2019 56(3):216-221 BACKGROUND: Epithelial ovarian cancer is the second most common gynecological cancer. Human Epididymis Protein 4 is a novel biomarker for ovarian cancer. This study aims to explore the role of HE4 in monitoring recurrence and prognostication of ovarian cancer by predicting overall survival (OS) and progression-free survival (PFS). MATERIALS AND METHODS: In total, 149 patients with ovarian carcinoma were enrolled in the study. Baseline and post-treatment 3 monthly biomarker levels were recorded. For analysis, patients were divided into primary debulking surgery (PDS) and interval debulking surgery (IDS) groups. Statistical analysis was done using SPSS 24. RESULTS: Median age of patients at diagnosis was 45 (19–75) years. Recurrence was seen in 68.5% (n = 102) patients. The sensitivity of serum HE4 in detecting recurrence was 85.3% (95%CI: 76.95%–91.5%) and specificity was 91.5% (95%CI: 89.5%–98.2%). A >80% decline in HE4 levels during treatment indicated a better PFS, which was statistically significant in both groups (P = 0.04 in PDS and P = <0.001 in IDS group). Multivariate analysis suggested that OS was influenced by optimal cytoreduction in both groups of patients and stage in the IDS group. On the contrary, PFS was influenced by stage and response in HE4 levels in both groups. CONCLUSION: HE4 levels have similar sensitivity but more specificity when compared with CA125 in diagnosing recurrent ovarian cancer. A >80% decline in HE4 levels during treatment predicts better PFS and can help in prognostication.

Community engaged breast cancer screening program in Kannur District, Kerala, India: A ray of hope for early diagnosis and treatment Neethu Ambali Parambil, Sairu Philip, Jaya Prasad Tripathy, Phinse M Philip, Karthickeyan Duraisamy, Satheesan Balasubramanian Indian Journal of Cancer 2019 56(3):222-227 INTRODUCTION: Community based programs can assist in early detection and improved survival of breast cancer. AIMS: To assess the feasibility and explore challenges of a district-wide door-to-door breast cancer screening program “ASWAS” conducted in Kannur district, Kerala, India from 2011 to 2014. METHODS: Aggregate data from survey records were collected in terms of the population screened, referred, diagnosed, and treated. Case records of breast cancer patients who were identified were reviewed and updated. In-depth interviews were conducted with program stakeholders. The contents of the interview were organized into a strength, weakness, opportunity and threat (SWOT) matrix to describe the screening program. RESULTS: A total of 1,049,410 eligible women above 30 years residing in 81 panchayats were visited door-to-door by 8,200 community volunteers; of them, 93% were screened using a symptom-risk factor checklist. Of those referred with symptoms (n = 5353), 81% attended the cancer camp. In total, 23 breast cancer cases were confirmed. 14 (61%) were in early stages, treated, and are disease free at 3-year follow-up. Those in the advanced stage and old age had poor outcomes. SWOT analysis identified political support, female volunteers, community engagement, dedicated fund for treatment, and teamwork as strengths. Weaknesses included poor healthcare access, maintaining volunteer motivation, and issues around sustainability. CONCLUSION: Community participation with the engagement of the health system and local self-government are required for implementing a comprehensive cancer screening strategy. Breast-cancer screening program using local volunteers for early detection is feasible in low-income settings, thereby improving survival.

Prognostic significance of residual nodal burden using lymph node ratio in locally advanced breast cancer after neoadjuvant chemotherapy Reshu Agarwal, Arun Philip, Keechilat Pavithran, Anupama Rajanbabu, Gaurav Goel, DK Vijaykumar Indian Journal of Cancer 2019 56(3):228-235 OBJECTIVE: To investigate the prognostic value of lymph node ratio (LNR) after neoadjuvant chemotherapy (NAC) according to breast cancer molecular subtypes. METHODS: From 2004 to 2014, patients with definitive surgery after NAC were identified. LNR was calculated for node positive patients who underwent axillary dissection and at least 10 nodes (LNT) were removed. Disease free and overall survivals were analysed using Kaplan-Meier test and compared using log rank test for ypN0-3, LNR categories (LNRC) ≤0.2 (low), 0.21-0.65 (intermediate), >0.65 (high), and single LNR cut-off value. RESULTS: Of 224 analysed patients: ypN0 72 (32.1%), ypN+ 152 (67.9%). Of 118 LNT ≥10 ypN+ patients LNRC: Low risk 48 (40.7%), intermediate risk 36 (30.5%), high risk 34 (28.8%). Factors significantly different in LNR categories were ypN (P < 0.001); extranodal extension (P < 0.001); present status of patients (P < 0.001); and disease status (P = 0.029). LNRC was inversely associated with 5-year DFS: Low 52.3%, intermediate 40%, and high 12.2% (log rank P < 0.001); and OS: Low 64.4%, intermediate 58.3%, and high 13.6% (log rank P < 0.001). Significant association of LNRC and DFS and OS were demonstrated in TNBC (P < 0.001) and HER2 subtypes (P = 0.045 and 0.005 respectively). A single value of LNR = 0.25 in node positive was found significant for DFS and OS in TNBC (P < 0.001) and Her2+ (P = 0.013 and P = 0.001 respectively) but not for HR+ (DFS: P = 0.132; OS: P = 0.144). CONCLUSION: Residual nodal disease after NAC analysed by LNRC or LNR = 0.25 cut-off value, is prognostic and can discriminate between favourable and unfavourable outcomes for TNBC and Her2+ breast cancers.

Use of interventional bronchoscopic treatment in small cell lung cancer Cengiz Ozdemir, Sinem N Sökücü, Ayşegül Berk, Levent Dalar Indian Journal of Cancer 2019 56(3):236-240 AIMS: Small cell lung cancer (SCLC) constitutes 15%-25% of all lung cancers. Their treatment approach is different from nonsmall cell lung cancer. Central airway obstruction develops at the time of diagnosis or eventually at some time as the disease progress. Quick relief of symptoms with chemotherapy will cause to postpone interventional bronchoscopy which divest patient from benefits of this procedure. There is a few data about the use of interventional bronchoscopy in SCLC. SUBJECTS AND METHODS: Between January 2005 and December 2012, rigid bronchoscopy under general anaesthesia was done in a total of 944 cases. Among them, 52 consecutive SCLC cases were evaluated retrospectively. STATISTICAL ANALYSIS: Survival was calculated from the date of application of therapeutic bronchoscopy using statistical software. RESULTS: From the 52 cases (41 males) mean age of the patients were 56,87 ± 10,16 (range 34-78). Most common obstruction areas were distal trachea and carina invasion involving both main bronchus (n: 12; 23%). Most common method used was mechanical desobstruction after coagulation with diode diode laser or APC. A total of 16 stents was applied to 15 of the cases from 52 cases (28.8%). Most common used stent was silicon Y stent (n: 11). Most common complication during the procedure was bleeding that was mild in 11 cases and massive in 1. One patient died during the procedure (1.9%). CONCLUSIONS: Multimodal interventional bronchoscopic methods seem to be a last option but may be useful in the management of advanced airway obstruction in the setting of SCLC. The choice of modality may be chosen depending upon individual patient characteristics as appropriate.

The impact of kidney function on colorectal cancer patients with localized and regional diseases: An observational study from Taiwan Sum-Fu Chiang, Jinn-Shiun Chen, Reiping Tang, Chien-Yuh Yeh, Pao-Shiu Hsieh, Wen-Sy Tsai, Jeng-Fu You, Hsin-Yuan Hung, Cheng-Chou Lai, Jr-Rung Lin, Jy-Ming Chiang Indian Journal of Cancer 2019 56(3):241-247 BACKGROUND: Impaired kidney function is associated with different diseases. However, its impact on colorectal cancer has not been clarified. In order to understand the effect of preoperative kidney function on the outcome of patients with cancer, we analyzed colorectal cancer patients with localized or regional diseases. MATERIALS AND METHODS: In total, 3731 stage I to III colorectal cancer (CRC) patients were analyzed in Chang Gung Memorial Hospital. Modification of Diet in Renal Disease (MDRD) formula was used for estimated glomerular filtration rate (eGFR). Receiver operating characteristic (ROC) analysis for kidney function cut-off value; Chi-square method, independent t test, or analysis of variance (ANOVA) method for clinicopathological factors; Kaplan–Meier method for disease-free survival (DFS); Cox proportional hazard model for multivariate analysis. RESULTS: Among colon cancer patients, low eGFR (MDRD <70) was associated with more male patients, T2 stage, patients without adjuvant chemotherapy, and patients with elevated creatinine level. Low eGFR is a significant risk factor only for stage III colon cancer (hazard ratio 1.70, 95% CI: 1.28–2.26; P < 0.001). Furthermore, postoperative adjuvant chemotherapy did not significantly increase 5-year DFS for both high and low eGFR groups in stage II patients (5 yrs DFS, 94.8% vs. 84.1%, P = 0.098 for high eGFR subgroup; and 75.0% vs. 75.8%, P = 0.379 for low eGFR subgroup). However, significant improvement of 5-yrs DFS after chemotherapy was found in low eGFR stage III colon cancer patients (64.7% vs. 39.4%, P < 0.001 for low eGFR subgroup). In contrast, no significant DFS difference was caused by chemotherapy for high eGFR stage III subgroup (70.5% vs. 63.9%, P = 0.110). CONCLUSIONS: Although low eGFR is an independent risk factor for stage III colon cancer. However, the adjuvant chemotherapy impacts on stage III colon cancer patients differently according to eGFR status.