Introduction Cancer cervix is the second most common cancer
among women worldwide and is the caus... more Introduction Cancer cervix is the second most common cancer among women worldwide and is the cause of largest number of cancer-related deaths among women in the developing countries. In India cervical cancer is the commonest cancer among women (126 000 new cases, 71 000 deaths around the year 2000). Due to the lack of any population based screening in India nearly 80% of the patients are detected at stage III or higher. There are trials that do not conclusively prove that currently recommended chemo-radiation will be equally effective in treating these large number of advanced cases. With the objectives to evaluate response and survival rates in patients with stage-III cervical cancer treated with immunotherapy concomitant with radiotherapy and compare the same with concomitant chemo-radiation and to evaluate the safety of concomitant immunotherapy and radiation this phase II trial was conducted by Chittaranjan National Cancer Institute from 2008 to 2010 and patients were followed up at 3 monthly intervals for 3 years. Methods Stage III cervical cancer patients were randomized to study arm (N = 104) or control arm (N = 105). In both arms the patients received standard external beam radiation followed by brachytherapy. In the study arm the patients received interferon-alpha 2b (3 mIU subcutaneously thrice a week for 4 weeks) and retinoic acid (40 mg/ day orally for 30 days) starting from first day of radiation. Patients in the control arm received cisplatin (40 mg/m2 once a week for 5 weeks) starting from first day of radiation. Patients were evaluated for response 1 month after completion of treatment. They were followed up every 3 months for 3 years or till death. Results The study arms were comparable for demographic and disease variables. Complete response was seen in 84.6% in study arm and 80.0% in control arm (P = 0.47). The 3 years overall survival was superior in the control arm (Log Rank analysis: X2 = 7.93; P = 0.005). The study and the control arms were comparable for disease-free survival (Log Rank analysis: X2 = 2.69; P = 0.10). The most frequently observed grade 3/4 toxicities were anemia, neutropenia and gastro-intestinal toxicities, which were significantly more frequent in chemo-radiation arm compared to immuno-radiation arm. Conclusions Immuno-radiation therapy had the same response rate and disease-free survival as chemo-radiation but better toxicity profile. The overall survival was inferior.
Globally, breast cancer is the most frequently diagnosed cancer among women. The major unresolved... more Globally, breast cancer is the most frequently diagnosed cancer among women. The major unresolved problems with metastatic breast cancer is recurrence after receiving objective response to chemotherapy, drug-induced side effects of first line chemotherapy and delayed response to second line of treatment. Unfortunately, very few options are available as third line treatment. It is clear that under such circumstances there is an urgent need for new and effective drugs. Phytochemicals are among the most promising chemopreventive treatment options for the management of cancer. Resveratrol (3,5,4'-trihydroxy-trans-stilbene), a non-flavonoid polyphenol present in several dietary sources, including grapes, berries, soy beans, pomegranate and peanuts, has been shown to possess a wide range of health benefits through its effect on a plethora of molecular targets.The present review encompasses the role of resveratrol and its natural/synthetic analogue in the light of their efficacy agains...
Indian Journal of Medical and Paediatric Oncology, Jan 10, 2013
The prospective study aimed to evaluate the effectiveness of Electron beam or HDR 192Ir Interstit... more The prospective study aimed to evaluate the effectiveness of Electron beam or HDR 192Ir Interstitial Implant used as a boost in breast Conservation cases after completion of EBRT. The two therapeutic modalities were compared in terms of the following parameters; i.e. cosmesis, optimization of tumor bed boost, local control, toxicity, and DFS. The EBRT dose used was 50 Gy in 25 fractions over 5 weeks time. Target delineation of boost treatment was done by CT scan or by high resolution USG. EBRT will be immediately followed by local boost at the primary tumor bearing site of breast with 8 to12 MeV electron beam to a dose of 15 Gy in 6 fractions (Arm A) or with HDR 192Ir interstitial brachytherapy to a dose of 15 Gy in 3 fractions at 6 hours apart (Arm B). The excellent cosmesis achieved with electron beam therapy in Arm A was found to be statistically significant (P = 0.025). Local relapse was absent in both the arms. One distant metastasis occurred in Arm A within 10 months of initiation of treatment and one distant metastasis in Arm B came out within 3 months of starting of therapy. The study has shown good cosmetic result with electron boost and 100% local control with both the technique. However if there is a more number of patients with longer period of follow up we could have got the actual picture to verify our results and assess long term survival data.
The Indian Journal of Medical Research, Jul 1, 2012
Background & objectives:Interferon alpha 2b (IFNα2b) has been reported to regulate several immune... more Background & objectives:Interferon alpha 2b (IFNα2b) has been reported to regulate several immune functions efficiently to enhance the cytotoxic activity of NK and T cells towards various forms of tumours. The objective of the present study was to evaluate the efficacy of IFNα2b in overcoming disease induced and/or treatment associated imunosuppression of tongue squamous cell carcinoma (TSCC) patients undergoing chemotherapy for better clinical outcome.Methods:Seven TSCC patients under cisplatin + 5-fluorouracil chemotherapy in combination with IFNα2b were assessed for various immunohaematological parameters before treatment, after chemotherapy and after IFNα2b therapy.Results:Deterioration of the haematological and immune responses was detected in immunosuppressed TSCC patients after chemotherapy. IFNα2b treatment led to a recovery in these parameters in most of the patients. Greater number of T/NK cells and enhanced secretion of type 1 cytokines were also noted. Haematological complications were reduced after completion of the therapy. Immune- and haematostimulation were also observed in patients with partial response. No positive clinical response was detected in one patient.Interpretation & conclusions:IFNα2b appears to be an effective immunostimulator having clinical impact to combat the immunosuppression in TSCC patients. Successful immunostimulation by IFNα2b may help TSCC patients in clinical improvement. The findings of this preliminary study need to be confirmed on a large number of patients with TSCC.
International Journal of Preventive Medicine, Sep 2, 2013
VIA is a simple, inexpensive test widely advocated for resource-limited settings. Major limitatio... more VIA is a simple, inexpensive test widely advocated for resource-limited settings. Major limitation of VIA is its low specificity. HPV DNA testing can be used to triage VIA-positive women if the facilities are available. The major concern for such strategy would be whether sample collection after acetic acid wash will alter HPV test characteristics. This study aimed to evaluate whether samples for HPV testing by Hybrid Capture 2 (HC2) technology can be collected immediately after VIA without altering test performance. Total 204 VIA-positive women were recruited. Cervical samples were collected for HC2 test before and after VIA at the same sitting by the same provider. The paired samples were analyzed at the same laboratory by the same technician in the same batch of testing. Agreement in HC2 results between pre-VIA and post-VIA samples was estimated using kappa statistics. All women had colposcopy and biopsies were obtained if colposcopy was suspicious of neoplasia. Sensitivity and specificity of HC2 test in detecting CIN2+ lesions were calculated using negative colposcopy or biopsy as the gold standard and were compared between the pre and post VIA samples. Almost perfect agreement in HC2 results (kappa=0.85) and RLU/Cut off ratios (correlation coefficient=0.92) was observed between samples collected before and after VIA. The sensitivity and specificity to detect CIN2+ lesions remained unaltered even when cervical samples were collected after VIA. This confirmed that acetic acid wash did not alter HC2 performance. Collection of samples for HC2 test is feasible immediately after VIA.
Current first-line treatment regimens combine surgical resection and chemoradiation for Glioblast... more Current first-line treatment regimens combine surgical resection and chemoradiation for Glioblastoma that provides a slight increase in overall survival. Age on its own should not be used as an exclusion criterion of glioblastoma multiforme (GBM) treatment, but performance should be factored heavily into the decision-making process for treatment planning. Despite aggressive initial treatment, most patients develop recurrent diseases which can be treated with re-resection, systemic treatment with targeted agents or cytotoxic chemotherapy, reirradiation, or radiosurgery. Research into novel therapies is investigating alternative temozolomide regimens, convection-enhanced delivery, immunotherapy, gene therapy, antiangiogenic agents, poly ADP ribose polymerase inhibitors, or cancer stem cell signaling pathways. Given the aggressive and resilient nature of GBM, continued efforts to better understand GBM pathophysiology are required to discover novel targets for future therapy.
A demonstration project was conducted to assess feasibility of implementing HPV detection-based c... more A demonstration project was conducted to assess feasibility of implementing HPV detection-based cervical cancer screening in primary care settings in India and to generate local evidence on feasibility and effectiveness of HPV detection in primary screening. The project was implemented by setting up screening clinics at primary health centers. Eligible women were screened by HPV DNA test (Hybrid capture 2). All samples were processed and tested in a single laboratory. Colposcopy services were provided to screen-positive women at the same community clinics. Project utilized services of community health workers for community mobilization, recall of screen-positive and disease-positive women. Women with ≥CIN2 diagnosis were treated at tertiary hospital. Totally, 44,110 women were screened and HPV positivity was 4.7 %. Compliance to recall of HC2-positive women for colposcopy was 78 %. Detection rate of CIN3+ by HPV test was 3.9/1,000 women. Compliance of women to treatment was 80.1 %. ...
Cisplatin (CDDP) is one of the first-line anticancer drugs; however, the major limitation of CDDP... more Cisplatin (CDDP) is one of the first-line anticancer drugs; however, the major limitation of CDDP therapy is development of nephrotoxicity (25-35% cases), whose precise mechanism mainly involves oxidative stress, inflammation and cell death. Therefore, in search of a potential chemoprotectant, an organovanadium complex, viz., vanadium(III)-L-cysteine (VC-III) was evaluated against CDDP-induced nephropathy in mice. CDDP was administered intraperitoneally (5 mg/kg b.w.) and VC-III was given by oral gavage (1 mg/kg b.w.) in concomitant and pre-treatment schedule. The results showed that VC-III administration reduced (p < 0.001) serum creatinine and blood urea nitrogen levels, suggesting amelioration of renal dysfunction. VC-III treatment also significantly (p < 0.001) prevented CDDP-induced generation of reactive oxygen species, reactive nitrogen species, and onset of lipid peroxidation in kidney tissues of the experimental mice. In addition, VC-III also substantially (p < 0.001) restored CDDP-induced depleted activities of the renal antioxidant enzymes such as, superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase, and glutathione (reduced) level. Furthermore, histopathological study also confirmed the renoprotective efficacy of VC-III. Western blotting analysis appended by immunohistochemical data showed that VC-III treatment quite effectively reduced the expression of proinflammatory mediators such as, NFκβ, COX-2 and IL-6. VC-III administration also stimulated Nrf2-mediated antioxidant defense system by promotion of downstream antioxidant enzymes, such as HO-1. Moreover, treatment with VC-III significantly (p < 0.001) enhanced CDDP-mediated cytotoxicity in MCF-7 and NCI-H520 human cancer cell lines. Thus, VC-III can serve as a suitable chemoprotectant and increase the therapeutic window of CDDP in cancer patients.
Hypoxia-inducible factor 1α (HIF-1α) plays a crucial role in facilitating tumor progression and m... more Hypoxia-inducible factor 1α (HIF-1α) plays a crucial role in facilitating tumor progression and metastasis. Reducing the levels of HIF-1α might therefore be an important anticancer strategy. This could be achieved by understanding the key cellular events involved in HIF-1α activation. Present study explored the effect of phenethyl isothiocyanate (PEITC), a natural isothiocyanate, found in cruciferous vegetables on the expression of HIF-1α and HSP90 in breast adenocarcinoma cell lines (MCF-7 and MDA-MB-231) under both normoxia and hypoxia. This study established the possible role of ROS in the up-regulation of these markers in breast cancer cells. PEITC induced nuclear accumulation of Nrf2, increased the activities of several antioxidant enzymes, and thus reduced the ROS burden of the tumor cells by acting as an indirect antioxidant. This resulted in the down-regulation of HSP90 and thereby HIF-1α expression. HSP90 was also found to be involved in the regulation of HIF-1α. A probable...
Haemoglobin levels and tissue oxygenation influence tumour outcome in carcinoma cervix radiothera... more Haemoglobin levels and tissue oxygenation influence tumour outcome in carcinoma cervix radiotherapy. The clinical impact of haemoglobin levels on acute normal tissue toxicity during radiation and interaction with chemotherapy in carcinoma of the cervix is underexplored. This paper aims to explore this issue. Treatment toxicity among 227 patients with squamous cell carcinoma of the cervix stages II B-IV A, receiving pelvic radiotherapy or chemoradiation at our institute, were studied prospectively. The baseline and weekly haemoglobin levels during treatment were recorded. Acute toxicities were recorded using Radiation Therapy Oncology Group (RTOG) acute toxicity and Common Terminology Criteria for Adverse Events (CTCAE) criteria, version 4. For the analysis, patients were divided into two groups, depending on nadir haemoglobin levels. A cut-off value for anaemia was selected at 12 gm/dL. Toxicity was compared between anaemic and non-anaemic groups. Patients on chemoradiation and having haemoglobin levels >12 gm/dL suffered significantly higher dermatitis (two-tailed p value = 0.0288) and vaginal mucositis (two-tailed p value = 0.0187) of at least RTOG acute toxicity grade 2, compared with the anaemic group. In contrast patients receiving radiotherapy alone did not experience any significantly greater mucocutaneous toxicity if haemoglobin was >12 gm/dL. Anaemia had significantly greater impact on malaise and neutropenia (two-tailed p value <0.0001) of CTCAE grade 1 and above among chemoradiation patients, as opposed to those receiving radiotherapy alone (two-tailed p values = 0.0012 for neutropenia and 0.0422 for malaise). Haemoglobin values >12 gm/dL significantly worsen acute mucocutaneous toxicity in locally advanced cervical cancer patients receiving chemoradiation. Similar effects are not observed in the absence of chemotherapy.
International Journal of Radiation Oncology*Biology*Physics, 2015
Because a combination of retinoic acid, interferon-alpha, and radiation therapy demonstrated syne... more Because a combination of retinoic acid, interferon-alpha, and radiation therapy demonstrated synergistic action and effectiveness to treat advanced cervical cancers in earlier studies, we designed this randomized phase 2 open-label trial to assess efficacy and safety of interferon alpha-2b (IFN) and 13-cis-retinoic acid (RA) administered concomitantly with radiation therapy (IFN-RA-radiation) to treat stage III cervical cancer. Stage III cervical cancer patients were randomized to study and control groups in a 1:1 ratio. All patients were treated with radiation therapy; study arm patients received IFN (3 × 10(6) IU subcutaneously) 3 times a week for 4 weeks and daily RA (40 mg orally) for 30 days starting on day 1 of radiation, whereas control arm patients received weekly cisplatinum (40 mg/m(2)) for 5 weeks during radiation. Patients were followed for 3 years. The primary endpoint was overall survival at 3 years. Patients in the study (n=104) and control (n=105) groups were comparable for clinicopathological characteristics, radiation therapy-related variables and treatment response. Proportions of disease-free patients in the study and control groups were 38.5% and 44.8%, respectively, after median follow-up of 29.2 months. Hazard ratios were 0.67 (95% confidence interval [CI]: 0.44-1.01) and 0.69 (95% CI: 0.44-1.06) for overall and disease-fee survival, respectively, comparing the study group to control, and demonstrated an inferior outcome with RA-IFN-radiation, although differences were statistically nonsignificant. Kaplan-Meier curves of disease-free and overall survival probabilities also showed inferior survival in the study group compared to those in the control. Acute toxicities of chemoradiation were significantly higher with 2 acute toxicity-related deaths. Treatment with RA-IFN-radiation did not demonstrate survival advantage over chemoradiation despite being less toxic. The trends predicted an inferior outcome with the RA-IFN combination.
A murine monoclonal antibody (mAb), 1C8 was developed against a novel glycoprotein NLGP and its u... more A murine monoclonal antibody (mAb), 1C8 was developed against a novel glycoprotein NLGP and its unique property to recognize carcinoembryonic antigen (CEA) was reported. Utilizing this CEA recognizing property, 1C8 is successful to restrict the growth of CEA(+) murine and human cancers both in vitro and in vivo. Here, we have thoroughly evaluated the toxicity profile of this mAb 1C8 on different physiological systems of both tumor-free and tumor-bearing Swiss and BALB/c mice. Effective concentration (25μg/mice) of 1C8 caused no behavioral changes in animals and no death was recorded. Moreover, little increase in the body and organ weights in all mice groups was noted. MAb 1C8 showed no adverse effect on the hematological system, but little hematostimulation was noticed, as evidenced by increased hemoglobin content, leukocyte count and lymphocyte numbers. Liver enzymes like alkaline phosphatase, SGOT, SGPT and nephrological products like urea and creatinine assessment confirmed no abnormalities in both hepatic and renal functions. Number of T cells, B cells, NK cells, macrophages and dendritic cells was upregulated in vivo by mAb treatment with significant downregulation of regulatory T cells. During this treatment serum levels of type 1 cytokines were upregulated over type 2 cytokines. This mAb 1C8 also did not induce any significant increase in antibody titer following treatment. Accumulated evidences from Swiss and BALB/c mice strongly suggest that this mAb 1C8 is completely safe, thus, can be recommended for further clinical trial for the therapy of CEA(+) tumors.
Chemotherapy is an integral part of modern day treatment regimen but anticancer drugs fail to dem... more Chemotherapy is an integral part of modern day treatment regimen but anticancer drugs fail to demarcate between cancerous and normal cells thereby causing severe form of systemic toxicity. Among which pulmonary toxicity is a dreadful complication developed in cancer patients upon cyclophosphamide (CP) therapy. Oxidative stress, fibrosis, and apoptosis are the major patho-mechanisms involved in CP-induced pulmonary toxicity. In the present study, we have synthesized Nano-Se, nanotechnology-based new form of elemental selenium which has significantly lower toxicity and acceptable bioavailability. In order to meet the need of effective drugs against CP-induced adverse effects, nano selenium (Nano-Se) was tested for its possible protective efficacy on CP-induced pulmonary toxicity and bone marrow toxicity. CP intoxication resulted in structural and functional lung impairment which was revealed by massive histopathological changes. Lung injury was associated with oxidative stress/lipid p...
In our experience, induction docetaxel, platinum, and fluorouracil (TPF) chemotherapy and sequent... more In our experience, induction docetaxel, platinum, and fluorouracil (TPF) chemotherapy and sequential chemoradiation in locally advanced head and neck cancer lowers compliance owing to their considerable toxicity. Most of our head and neck cancer patients have locally advanced disease at presentation. Physicians frequently prefer paclitaxel-cisplatin induction chemotherapy instead, because of better patient tolerance. A total of 207 locally advanced head and neck cancer patients receiving paclitaxel and cisplatin prior to chemoradiation from November 2010 to October 2013 were studied retrospectively. Parameters like febrile neutropaenia, treatment compliance, and response rates were compared to our institutional retrospective data with TPF chemotherapy. Response was assessed by Response Evaluation Criteria in Solid Tumours (Recist) version 1.1. Toxicity was assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 during chemotherapy. Radiation Therapy Oncology G...
To assess impact of relative total dose intensity (RTDI) on clinical benefit among patients with ... more To assess impact of relative total dose intensity (RTDI) on clinical benefit among patients with locally advanced carcinoma gall bladder receiving gemcitabine-cisplatin (GemCis). Comparison of clinical benefit among patients receiving variable RTDI was the primary objective. The secondary objective was an impact of RTDI on chemotherapy toxicity. One-hundred twenty-one patients with locally advanced inoperable carcinoma gall bladder undergoing chemotherapy with three weekly gemcitabine-cisplatin chemotherapies (gemcitabine 1000 mg/m(2) on day 1 and 8, cisplatin 70 mg/m(2) on day 1) were studied. Clinical benefit and treatment toxicity was assessed. Total dose of chemotherapy and relative total dose intensity, the proportion of planned dose actually received was calculated. RTDI of at least 50 % conferred substantial clinical benefit compared to lower RTDI (75.49 vs. 21.05 %). RTDI above 50-59 % did not improve clinical benefit; two-tailed p values of RTDI >60 % vs. RTDI >50 % a...
Cancer immunology, immunotherapy : CII, Jan 17, 2015
The aim of this study was to understand the association of human papillomavirus (HPV) type 16/18 ... more The aim of this study was to understand the association of human papillomavirus (HPV) type 16/18 infection and polymorphisms in the HLA-DQB1 (rs6457617) and IL-1β -511 (rs16944) loci with the development of uterine cervical cancer (CaCx). The distribution of HLA-DQB1 G > A and IL-1β -511 C/T polymorphisms was determined in HPV-negative cervical swabs from normal women (N = 111) and compared with cervical swabs of HPV-cleared normal women (once HPV infected followed by natural clearance of the infection, N = 86), HPV16/18-positive cervical intraepithelial neoplasia (CIN, N = 41) and CaCx biopsies (N = 107). The A-allele containing genotypes (i.e. G/A and A/A) of HLA-DQB1 was significantly associated with CaCx compared with HPV-negative [OR = 2.56(1.42-4.62), p = 0.001] or HPV-cleared [OR = 2.07(1.12-3.87), p = 0.01] normal women, whereas the T-allele containing genotypes (i.e. C/T and T/T) of IL-1β showed increased risk of CIN [OR = 3.68(0.97-16.35), p = 0.03; OR = 3.59(0.92-16.38...
Introduction Cancer cervix is the second most common cancer
among women worldwide and is the caus... more Introduction Cancer cervix is the second most common cancer among women worldwide and is the cause of largest number of cancer-related deaths among women in the developing countries. In India cervical cancer is the commonest cancer among women (126 000 new cases, 71 000 deaths around the year 2000). Due to the lack of any population based screening in India nearly 80% of the patients are detected at stage III or higher. There are trials that do not conclusively prove that currently recommended chemo-radiation will be equally effective in treating these large number of advanced cases. With the objectives to evaluate response and survival rates in patients with stage-III cervical cancer treated with immunotherapy concomitant with radiotherapy and compare the same with concomitant chemo-radiation and to evaluate the safety of concomitant immunotherapy and radiation this phase II trial was conducted by Chittaranjan National Cancer Institute from 2008 to 2010 and patients were followed up at 3 monthly intervals for 3 years. Methods Stage III cervical cancer patients were randomized to study arm (N = 104) or control arm (N = 105). In both arms the patients received standard external beam radiation followed by brachytherapy. In the study arm the patients received interferon-alpha 2b (3 mIU subcutaneously thrice a week for 4 weeks) and retinoic acid (40 mg/ day orally for 30 days) starting from first day of radiation. Patients in the control arm received cisplatin (40 mg/m2 once a week for 5 weeks) starting from first day of radiation. Patients were evaluated for response 1 month after completion of treatment. They were followed up every 3 months for 3 years or till death. Results The study arms were comparable for demographic and disease variables. Complete response was seen in 84.6% in study arm and 80.0% in control arm (P = 0.47). The 3 years overall survival was superior in the control arm (Log Rank analysis: X2 = 7.93; P = 0.005). The study and the control arms were comparable for disease-free survival (Log Rank analysis: X2 = 2.69; P = 0.10). The most frequently observed grade 3/4 toxicities were anemia, neutropenia and gastro-intestinal toxicities, which were significantly more frequent in chemo-radiation arm compared to immuno-radiation arm. Conclusions Immuno-radiation therapy had the same response rate and disease-free survival as chemo-radiation but better toxicity profile. The overall survival was inferior.
Globally, breast cancer is the most frequently diagnosed cancer among women. The major unresolved... more Globally, breast cancer is the most frequently diagnosed cancer among women. The major unresolved problems with metastatic breast cancer is recurrence after receiving objective response to chemotherapy, drug-induced side effects of first line chemotherapy and delayed response to second line of treatment. Unfortunately, very few options are available as third line treatment. It is clear that under such circumstances there is an urgent need for new and effective drugs. Phytochemicals are among the most promising chemopreventive treatment options for the management of cancer. Resveratrol (3,5,4'-trihydroxy-trans-stilbene), a non-flavonoid polyphenol present in several dietary sources, including grapes, berries, soy beans, pomegranate and peanuts, has been shown to possess a wide range of health benefits through its effect on a plethora of molecular targets.The present review encompasses the role of resveratrol and its natural/synthetic analogue in the light of their efficacy agains...
Indian Journal of Medical and Paediatric Oncology, Jan 10, 2013
The prospective study aimed to evaluate the effectiveness of Electron beam or HDR 192Ir Interstit... more The prospective study aimed to evaluate the effectiveness of Electron beam or HDR 192Ir Interstitial Implant used as a boost in breast Conservation cases after completion of EBRT. The two therapeutic modalities were compared in terms of the following parameters; i.e. cosmesis, optimization of tumor bed boost, local control, toxicity, and DFS. The EBRT dose used was 50 Gy in 25 fractions over 5 weeks time. Target delineation of boost treatment was done by CT scan or by high resolution USG. EBRT will be immediately followed by local boost at the primary tumor bearing site of breast with 8 to12 MeV electron beam to a dose of 15 Gy in 6 fractions (Arm A) or with HDR 192Ir interstitial brachytherapy to a dose of 15 Gy in 3 fractions at 6 hours apart (Arm B). The excellent cosmesis achieved with electron beam therapy in Arm A was found to be statistically significant (P = 0.025). Local relapse was absent in both the arms. One distant metastasis occurred in Arm A within 10 months of initiation of treatment and one distant metastasis in Arm B came out within 3 months of starting of therapy. The study has shown good cosmetic result with electron boost and 100% local control with both the technique. However if there is a more number of patients with longer period of follow up we could have got the actual picture to verify our results and assess long term survival data.
The Indian Journal of Medical Research, Jul 1, 2012
Background & objectives:Interferon alpha 2b (IFNα2b) has been reported to regulate several immune... more Background & objectives:Interferon alpha 2b (IFNα2b) has been reported to regulate several immune functions efficiently to enhance the cytotoxic activity of NK and T cells towards various forms of tumours. The objective of the present study was to evaluate the efficacy of IFNα2b in overcoming disease induced and/or treatment associated imunosuppression of tongue squamous cell carcinoma (TSCC) patients undergoing chemotherapy for better clinical outcome.Methods:Seven TSCC patients under cisplatin + 5-fluorouracil chemotherapy in combination with IFNα2b were assessed for various immunohaematological parameters before treatment, after chemotherapy and after IFNα2b therapy.Results:Deterioration of the haematological and immune responses was detected in immunosuppressed TSCC patients after chemotherapy. IFNα2b treatment led to a recovery in these parameters in most of the patients. Greater number of T/NK cells and enhanced secretion of type 1 cytokines were also noted. Haematological complications were reduced after completion of the therapy. Immune- and haematostimulation were also observed in patients with partial response. No positive clinical response was detected in one patient.Interpretation & conclusions:IFNα2b appears to be an effective immunostimulator having clinical impact to combat the immunosuppression in TSCC patients. Successful immunostimulation by IFNα2b may help TSCC patients in clinical improvement. The findings of this preliminary study need to be confirmed on a large number of patients with TSCC.
International Journal of Preventive Medicine, Sep 2, 2013
VIA is a simple, inexpensive test widely advocated for resource-limited settings. Major limitatio... more VIA is a simple, inexpensive test widely advocated for resource-limited settings. Major limitation of VIA is its low specificity. HPV DNA testing can be used to triage VIA-positive women if the facilities are available. The major concern for such strategy would be whether sample collection after acetic acid wash will alter HPV test characteristics. This study aimed to evaluate whether samples for HPV testing by Hybrid Capture 2 (HC2) technology can be collected immediately after VIA without altering test performance. Total 204 VIA-positive women were recruited. Cervical samples were collected for HC2 test before and after VIA at the same sitting by the same provider. The paired samples were analyzed at the same laboratory by the same technician in the same batch of testing. Agreement in HC2 results between pre-VIA and post-VIA samples was estimated using kappa statistics. All women had colposcopy and biopsies were obtained if colposcopy was suspicious of neoplasia. Sensitivity and specificity of HC2 test in detecting CIN2+ lesions were calculated using negative colposcopy or biopsy as the gold standard and were compared between the pre and post VIA samples. Almost perfect agreement in HC2 results (kappa=0.85) and RLU/Cut off ratios (correlation coefficient=0.92) was observed between samples collected before and after VIA. The sensitivity and specificity to detect CIN2+ lesions remained unaltered even when cervical samples were collected after VIA. This confirmed that acetic acid wash did not alter HC2 performance. Collection of samples for HC2 test is feasible immediately after VIA.
Current first-line treatment regimens combine surgical resection and chemoradiation for Glioblast... more Current first-line treatment regimens combine surgical resection and chemoradiation for Glioblastoma that provides a slight increase in overall survival. Age on its own should not be used as an exclusion criterion of glioblastoma multiforme (GBM) treatment, but performance should be factored heavily into the decision-making process for treatment planning. Despite aggressive initial treatment, most patients develop recurrent diseases which can be treated with re-resection, systemic treatment with targeted agents or cytotoxic chemotherapy, reirradiation, or radiosurgery. Research into novel therapies is investigating alternative temozolomide regimens, convection-enhanced delivery, immunotherapy, gene therapy, antiangiogenic agents, poly ADP ribose polymerase inhibitors, or cancer stem cell signaling pathways. Given the aggressive and resilient nature of GBM, continued efforts to better understand GBM pathophysiology are required to discover novel targets for future therapy.
A demonstration project was conducted to assess feasibility of implementing HPV detection-based c... more A demonstration project was conducted to assess feasibility of implementing HPV detection-based cervical cancer screening in primary care settings in India and to generate local evidence on feasibility and effectiveness of HPV detection in primary screening. The project was implemented by setting up screening clinics at primary health centers. Eligible women were screened by HPV DNA test (Hybrid capture 2). All samples were processed and tested in a single laboratory. Colposcopy services were provided to screen-positive women at the same community clinics. Project utilized services of community health workers for community mobilization, recall of screen-positive and disease-positive women. Women with ≥CIN2 diagnosis were treated at tertiary hospital. Totally, 44,110 women were screened and HPV positivity was 4.7 %. Compliance to recall of HC2-positive women for colposcopy was 78 %. Detection rate of CIN3+ by HPV test was 3.9/1,000 women. Compliance of women to treatment was 80.1 %. ...
Cisplatin (CDDP) is one of the first-line anticancer drugs; however, the major limitation of CDDP... more Cisplatin (CDDP) is one of the first-line anticancer drugs; however, the major limitation of CDDP therapy is development of nephrotoxicity (25-35% cases), whose precise mechanism mainly involves oxidative stress, inflammation and cell death. Therefore, in search of a potential chemoprotectant, an organovanadium complex, viz., vanadium(III)-L-cysteine (VC-III) was evaluated against CDDP-induced nephropathy in mice. CDDP was administered intraperitoneally (5 mg/kg b.w.) and VC-III was given by oral gavage (1 mg/kg b.w.) in concomitant and pre-treatment schedule. The results showed that VC-III administration reduced (p < 0.001) serum creatinine and blood urea nitrogen levels, suggesting amelioration of renal dysfunction. VC-III treatment also significantly (p < 0.001) prevented CDDP-induced generation of reactive oxygen species, reactive nitrogen species, and onset of lipid peroxidation in kidney tissues of the experimental mice. In addition, VC-III also substantially (p < 0.001) restored CDDP-induced depleted activities of the renal antioxidant enzymes such as, superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase, and glutathione (reduced) level. Furthermore, histopathological study also confirmed the renoprotective efficacy of VC-III. Western blotting analysis appended by immunohistochemical data showed that VC-III treatment quite effectively reduced the expression of proinflammatory mediators such as, NFκβ, COX-2 and IL-6. VC-III administration also stimulated Nrf2-mediated antioxidant defense system by promotion of downstream antioxidant enzymes, such as HO-1. Moreover, treatment with VC-III significantly (p < 0.001) enhanced CDDP-mediated cytotoxicity in MCF-7 and NCI-H520 human cancer cell lines. Thus, VC-III can serve as a suitable chemoprotectant and increase the therapeutic window of CDDP in cancer patients.
Hypoxia-inducible factor 1α (HIF-1α) plays a crucial role in facilitating tumor progression and m... more Hypoxia-inducible factor 1α (HIF-1α) plays a crucial role in facilitating tumor progression and metastasis. Reducing the levels of HIF-1α might therefore be an important anticancer strategy. This could be achieved by understanding the key cellular events involved in HIF-1α activation. Present study explored the effect of phenethyl isothiocyanate (PEITC), a natural isothiocyanate, found in cruciferous vegetables on the expression of HIF-1α and HSP90 in breast adenocarcinoma cell lines (MCF-7 and MDA-MB-231) under both normoxia and hypoxia. This study established the possible role of ROS in the up-regulation of these markers in breast cancer cells. PEITC induced nuclear accumulation of Nrf2, increased the activities of several antioxidant enzymes, and thus reduced the ROS burden of the tumor cells by acting as an indirect antioxidant. This resulted in the down-regulation of HSP90 and thereby HIF-1α expression. HSP90 was also found to be involved in the regulation of HIF-1α. A probable...
Haemoglobin levels and tissue oxygenation influence tumour outcome in carcinoma cervix radiothera... more Haemoglobin levels and tissue oxygenation influence tumour outcome in carcinoma cervix radiotherapy. The clinical impact of haemoglobin levels on acute normal tissue toxicity during radiation and interaction with chemotherapy in carcinoma of the cervix is underexplored. This paper aims to explore this issue. Treatment toxicity among 227 patients with squamous cell carcinoma of the cervix stages II B-IV A, receiving pelvic radiotherapy or chemoradiation at our institute, were studied prospectively. The baseline and weekly haemoglobin levels during treatment were recorded. Acute toxicities were recorded using Radiation Therapy Oncology Group (RTOG) acute toxicity and Common Terminology Criteria for Adverse Events (CTCAE) criteria, version 4. For the analysis, patients were divided into two groups, depending on nadir haemoglobin levels. A cut-off value for anaemia was selected at 12 gm/dL. Toxicity was compared between anaemic and non-anaemic groups. Patients on chemoradiation and having haemoglobin levels >12 gm/dL suffered significantly higher dermatitis (two-tailed p value = 0.0288) and vaginal mucositis (two-tailed p value = 0.0187) of at least RTOG acute toxicity grade 2, compared with the anaemic group. In contrast patients receiving radiotherapy alone did not experience any significantly greater mucocutaneous toxicity if haemoglobin was >12 gm/dL. Anaemia had significantly greater impact on malaise and neutropenia (two-tailed p value <0.0001) of CTCAE grade 1 and above among chemoradiation patients, as opposed to those receiving radiotherapy alone (two-tailed p values = 0.0012 for neutropenia and 0.0422 for malaise). Haemoglobin values >12 gm/dL significantly worsen acute mucocutaneous toxicity in locally advanced cervical cancer patients receiving chemoradiation. Similar effects are not observed in the absence of chemotherapy.
International Journal of Radiation Oncology*Biology*Physics, 2015
Because a combination of retinoic acid, interferon-alpha, and radiation therapy demonstrated syne... more Because a combination of retinoic acid, interferon-alpha, and radiation therapy demonstrated synergistic action and effectiveness to treat advanced cervical cancers in earlier studies, we designed this randomized phase 2 open-label trial to assess efficacy and safety of interferon alpha-2b (IFN) and 13-cis-retinoic acid (RA) administered concomitantly with radiation therapy (IFN-RA-radiation) to treat stage III cervical cancer. Stage III cervical cancer patients were randomized to study and control groups in a 1:1 ratio. All patients were treated with radiation therapy; study arm patients received IFN (3 × 10(6) IU subcutaneously) 3 times a week for 4 weeks and daily RA (40 mg orally) for 30 days starting on day 1 of radiation, whereas control arm patients received weekly cisplatinum (40 mg/m(2)) for 5 weeks during radiation. Patients were followed for 3 years. The primary endpoint was overall survival at 3 years. Patients in the study (n=104) and control (n=105) groups were comparable for clinicopathological characteristics, radiation therapy-related variables and treatment response. Proportions of disease-free patients in the study and control groups were 38.5% and 44.8%, respectively, after median follow-up of 29.2 months. Hazard ratios were 0.67 (95% confidence interval [CI]: 0.44-1.01) and 0.69 (95% CI: 0.44-1.06) for overall and disease-fee survival, respectively, comparing the study group to control, and demonstrated an inferior outcome with RA-IFN-radiation, although differences were statistically nonsignificant. Kaplan-Meier curves of disease-free and overall survival probabilities also showed inferior survival in the study group compared to those in the control. Acute toxicities of chemoradiation were significantly higher with 2 acute toxicity-related deaths. Treatment with RA-IFN-radiation did not demonstrate survival advantage over chemoradiation despite being less toxic. The trends predicted an inferior outcome with the RA-IFN combination.
A murine monoclonal antibody (mAb), 1C8 was developed against a novel glycoprotein NLGP and its u... more A murine monoclonal antibody (mAb), 1C8 was developed against a novel glycoprotein NLGP and its unique property to recognize carcinoembryonic antigen (CEA) was reported. Utilizing this CEA recognizing property, 1C8 is successful to restrict the growth of CEA(+) murine and human cancers both in vitro and in vivo. Here, we have thoroughly evaluated the toxicity profile of this mAb 1C8 on different physiological systems of both tumor-free and tumor-bearing Swiss and BALB/c mice. Effective concentration (25μg/mice) of 1C8 caused no behavioral changes in animals and no death was recorded. Moreover, little increase in the body and organ weights in all mice groups was noted. MAb 1C8 showed no adverse effect on the hematological system, but little hematostimulation was noticed, as evidenced by increased hemoglobin content, leukocyte count and lymphocyte numbers. Liver enzymes like alkaline phosphatase, SGOT, SGPT and nephrological products like urea and creatinine assessment confirmed no abnormalities in both hepatic and renal functions. Number of T cells, B cells, NK cells, macrophages and dendritic cells was upregulated in vivo by mAb treatment with significant downregulation of regulatory T cells. During this treatment serum levels of type 1 cytokines were upregulated over type 2 cytokines. This mAb 1C8 also did not induce any significant increase in antibody titer following treatment. Accumulated evidences from Swiss and BALB/c mice strongly suggest that this mAb 1C8 is completely safe, thus, can be recommended for further clinical trial for the therapy of CEA(+) tumors.
Chemotherapy is an integral part of modern day treatment regimen but anticancer drugs fail to dem... more Chemotherapy is an integral part of modern day treatment regimen but anticancer drugs fail to demarcate between cancerous and normal cells thereby causing severe form of systemic toxicity. Among which pulmonary toxicity is a dreadful complication developed in cancer patients upon cyclophosphamide (CP) therapy. Oxidative stress, fibrosis, and apoptosis are the major patho-mechanisms involved in CP-induced pulmonary toxicity. In the present study, we have synthesized Nano-Se, nanotechnology-based new form of elemental selenium which has significantly lower toxicity and acceptable bioavailability. In order to meet the need of effective drugs against CP-induced adverse effects, nano selenium (Nano-Se) was tested for its possible protective efficacy on CP-induced pulmonary toxicity and bone marrow toxicity. CP intoxication resulted in structural and functional lung impairment which was revealed by massive histopathological changes. Lung injury was associated with oxidative stress/lipid p...
In our experience, induction docetaxel, platinum, and fluorouracil (TPF) chemotherapy and sequent... more In our experience, induction docetaxel, platinum, and fluorouracil (TPF) chemotherapy and sequential chemoradiation in locally advanced head and neck cancer lowers compliance owing to their considerable toxicity. Most of our head and neck cancer patients have locally advanced disease at presentation. Physicians frequently prefer paclitaxel-cisplatin induction chemotherapy instead, because of better patient tolerance. A total of 207 locally advanced head and neck cancer patients receiving paclitaxel and cisplatin prior to chemoradiation from November 2010 to October 2013 were studied retrospectively. Parameters like febrile neutropaenia, treatment compliance, and response rates were compared to our institutional retrospective data with TPF chemotherapy. Response was assessed by Response Evaluation Criteria in Solid Tumours (Recist) version 1.1. Toxicity was assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 during chemotherapy. Radiation Therapy Oncology G...
To assess impact of relative total dose intensity (RTDI) on clinical benefit among patients with ... more To assess impact of relative total dose intensity (RTDI) on clinical benefit among patients with locally advanced carcinoma gall bladder receiving gemcitabine-cisplatin (GemCis). Comparison of clinical benefit among patients receiving variable RTDI was the primary objective. The secondary objective was an impact of RTDI on chemotherapy toxicity. One-hundred twenty-one patients with locally advanced inoperable carcinoma gall bladder undergoing chemotherapy with three weekly gemcitabine-cisplatin chemotherapies (gemcitabine 1000 mg/m(2) on day 1 and 8, cisplatin 70 mg/m(2) on day 1) were studied. Clinical benefit and treatment toxicity was assessed. Total dose of chemotherapy and relative total dose intensity, the proportion of planned dose actually received was calculated. RTDI of at least 50 % conferred substantial clinical benefit compared to lower RTDI (75.49 vs. 21.05 %). RTDI above 50-59 % did not improve clinical benefit; two-tailed p values of RTDI >60 % vs. RTDI >50 % a...
Cancer immunology, immunotherapy : CII, Jan 17, 2015
The aim of this study was to understand the association of human papillomavirus (HPV) type 16/18 ... more The aim of this study was to understand the association of human papillomavirus (HPV) type 16/18 infection and polymorphisms in the HLA-DQB1 (rs6457617) and IL-1β -511 (rs16944) loci with the development of uterine cervical cancer (CaCx). The distribution of HLA-DQB1 G > A and IL-1β -511 C/T polymorphisms was determined in HPV-negative cervical swabs from normal women (N = 111) and compared with cervical swabs of HPV-cleared normal women (once HPV infected followed by natural clearance of the infection, N = 86), HPV16/18-positive cervical intraepithelial neoplasia (CIN, N = 41) and CaCx biopsies (N = 107). The A-allele containing genotypes (i.e. G/A and A/A) of HLA-DQB1 was significantly associated with CaCx compared with HPV-negative [OR = 2.56(1.42-4.62), p = 0.001] or HPV-cleared [OR = 2.07(1.12-3.87), p = 0.01] normal women, whereas the T-allele containing genotypes (i.e. C/T and T/T) of IL-1β showed increased risk of CIN [OR = 3.68(0.97-16.35), p = 0.03; OR = 3.59(0.92-16.38...
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Papers by Jaydip Biswas
among women worldwide and is the cause of largest number of
cancer-related deaths among women in the developing countries.
In India cervical cancer is the commonest cancer among women
(126 000 new cases, 71 000 deaths around the year 2000). Due to
the lack of any population based screening in India nearly 80% of
the patients are detected at stage III or higher. There are trials
that do not conclusively prove that currently recommended
chemo-radiation will be equally effective in treating these large
number of advanced cases. With the objectives to evaluate
response and survival rates in patients with stage-III cervical
cancer treated with immunotherapy concomitant with
radiotherapy and compare the same with concomitant
chemo-radiation and to evaluate the safety of concomitant
immunotherapy and radiation this phase II trial was conducted by
Chittaranjan National Cancer Institute from 2008 to 2010 and
patients were followed up at 3 monthly intervals for 3 years.
Methods Stage III cervical cancer patients were randomized to study
arm (N = 104) or control arm (N = 105). In both arms the patients
received standard external beam radiation followed by brachytherapy.
In the study arm the patients received interferon-alpha 2b (3 mIU
subcutaneously thrice a week for 4 weeks) and retinoic acid (40 mg/
day orally for 30 days) starting from first day of radiation. Patients in
the control arm received cisplatin (40 mg/m2 once a week for
5 weeks) starting from first day of radiation. Patients were evaluated
for response 1 month after completion of treatment. They were
followed up every 3 months for 3 years or till death.
Results The study arms were comparable for demographic and
disease variables. Complete response was seen in 84.6% in study
arm and 80.0% in control arm (P = 0.47). The 3 years overall
survival was superior in the control arm (Log Rank analysis:
X2 = 7.93; P = 0.005). The study and the control arms were
comparable for disease-free survival (Log Rank analysis:
X2 = 2.69; P = 0.10). The most frequently observed grade 3/4
toxicities were anemia, neutropenia and gastro-intestinal toxicities,
which were significantly more frequent in chemo-radiation arm
compared to immuno-radiation arm.
Conclusions Immuno-radiation therapy had the same response
rate and disease-free survival as chemo-radiation but better
toxicity profile. The overall survival was inferior.
among women worldwide and is the cause of largest number of
cancer-related deaths among women in the developing countries.
In India cervical cancer is the commonest cancer among women
(126 000 new cases, 71 000 deaths around the year 2000). Due to
the lack of any population based screening in India nearly 80% of
the patients are detected at stage III or higher. There are trials
that do not conclusively prove that currently recommended
chemo-radiation will be equally effective in treating these large
number of advanced cases. With the objectives to evaluate
response and survival rates in patients with stage-III cervical
cancer treated with immunotherapy concomitant with
radiotherapy and compare the same with concomitant
chemo-radiation and to evaluate the safety of concomitant
immunotherapy and radiation this phase II trial was conducted by
Chittaranjan National Cancer Institute from 2008 to 2010 and
patients were followed up at 3 monthly intervals for 3 years.
Methods Stage III cervical cancer patients were randomized to study
arm (N = 104) or control arm (N = 105). In both arms the patients
received standard external beam radiation followed by brachytherapy.
In the study arm the patients received interferon-alpha 2b (3 mIU
subcutaneously thrice a week for 4 weeks) and retinoic acid (40 mg/
day orally for 30 days) starting from first day of radiation. Patients in
the control arm received cisplatin (40 mg/m2 once a week for
5 weeks) starting from first day of radiation. Patients were evaluated
for response 1 month after completion of treatment. They were
followed up every 3 months for 3 years or till death.
Results The study arms were comparable for demographic and
disease variables. Complete response was seen in 84.6% in study
arm and 80.0% in control arm (P = 0.47). The 3 years overall
survival was superior in the control arm (Log Rank analysis:
X2 = 7.93; P = 0.005). The study and the control arms were
comparable for disease-free survival (Log Rank analysis:
X2 = 2.69; P = 0.10). The most frequently observed grade 3/4
toxicities were anemia, neutropenia and gastro-intestinal toxicities,
which were significantly more frequent in chemo-radiation arm
compared to immuno-radiation arm.
Conclusions Immuno-radiation therapy had the same response
rate and disease-free survival as chemo-radiation but better
toxicity profile. The overall survival was inferior.