• Asian Pacific Journal of Cancer Prevention
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• v.15 no.2
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• pp.899-904
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• 2014

Concurrent chemo-radiation (CRT) has been established as the standard of care for non-metastatic loco-regionally advanced nasopharyngeal carcinoma (NPC) but recently the addition of induction chemotherapy in the already established regimen has presented an attractive multidisciplinary approach. This retrospective study was carried out to evaluate the efficacy of induction chemotherapy (IC) followed by CRT for the management of loco-regionally advanced NPC. Between July 2005 and September 2010, 99 patients were treated with cisplatin based IC followed by CRT. Induction chemotherapy included a 2 drug combination; intravenous gemcitabine $1000mg/m^2$ on day 1 and 8 and cisplatin $75mg/m^2$ on day 1 only. Radiotherapy (RT) was given as a phase treatment to a total dose of 70 Gy in 35 fractions. Concurrent cisplatin ($75mg/m^2$) was administered to all patients on days 1, 22 and 43. All patients were evaluated for tumor response and adverse effects after IC and 6 weeks after the completion of the treatment protocol. Statistical analysis was performed using SPSS version 17 and Kaplan Meier estimates were applied to project survival. Median follow-up duration was 20 months. The 5-year overall survival (OS), loco regional control (LRC) and relapse free survival (RFS) rates were 71%, 73% and 50%respectively. Acute grade 4 toxicity related to induction chemotherapy and concurrent chemo-radiation was 4% and 2% respectively, with only 3 toxicity-related hospital admissions. We conclude that induction gemcitabine and cisplatin followed by chemo-radiation is a safe and effective regimen in management of nasopharyngeal carcinoma, meriting further investigation in randomized clinical trials.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.3
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• pp.1111-1116
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• 2015

Background: To investigate the relationship between pathologic tumor response to concurrent chemoradiotherapy and variation of serum VEGF in patients with esophageal cancer. Materials and Methods: Forty six patients with esophageal cancer who were treated with concurrent chemo-radiotherapy were enrolled. Endoscopic and pathologic examination was conducted before and four weeks afterwards. Serum level of VEGF was documented before, four weeks later and after chemo-radiotherapy. The relationship between pathologic response and the variation of serum level of VEGF and its influence on the prognosis were investigated. Results: Serum level of VEGF decreased remarkably during and after chemo-radiotherapy in patients whose pathologic response was severe (F=5.393, 4.587, P(0.05). There were no statistical differences of serum VEGF level before, during and after chemo-radiotherapy for patients whose pathologic response was moderate or mild. There were 18 (85.7%), 7 (53.8%) and 6 patients (50.0%) whose serum VEGF level dropped in the severe, moderate and mild group, respectively, with significant differences among these groups (p=0.046). Two year survival rates of patients with severe, moderate and mild pathologic response were 61.9%, 53.8% and 33.3% respectively, and no statistically difference between severe and mild group regarding OS (p=0.245) was tested. Conclusions: Tumor pathologic response during chemo-radiotherapy and the changes of serum VEGF lever could predict curative effects of chemo-radiotherapy in patients with esophageal cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.11
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• pp.4723-4726
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• 2015

Background: The survival of patients with hypopharyngeal cancer is low amongst head and neck cancer cases. The incidence rates of hypopharyngeal cancers in our population are amongst the highest in the world and there are limited data available on the literature on varied responses to first course of treatment with radiotherapy (RT) and concurrent chemo-radiotherapy (CRT) in our population. Materials and Methods: Clinical characteristics and initial responses to treatment in patients who had received radiotherapy and chemo-radiotherapy in a regional cancer center from January 2010 to December 2013 were evaluated. The data were obtained from the hospital cancer registry, and analysis was carried using descriptive statistics. Pearson's chi-square was used to test for differences in the variables and p<0.05 was considered statistically significant. Results: A total of 554 patients were included in the analysis, 411 (74.2%) receiving RT and 143 (25.8%) being given CRT. There was significantly lower number of patients above 70 years with a higher proportion of patients below 50 years who had received CRT (p<0.05). Some 79.3% and 84.6% of patients in the RT and CRT groups respectively presented with a favorable performance status, and in the RT group 240 (58.4%) showed complete response (CR), and in the CRT group 103 (72.0%) showed CR at the first follow-up (p<0.05). Conclusions: Concurrent chemo-radiotherapy gives better short term response to treatment in locally advanced hypopharyngeal cancers.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.17
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• pp.7371-7375
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• 2014

Background: Concurrent chemo-radiotherapy is the recommended standard treatment modality for patients with locally advanced lung cancer. The purpose of three-dimensional conformal radiotherapy (3DCRT) is to minimize normal tissue damage while a high dose can be delivered to the tumor. The most common dose limiting side effect of thoracic RT is radiation pneumonia (RP). In this study we evaluated the relationship between dose-volume histogram parameters and radiation pneumonitis. This study targeted prediction of the possible development of RP and evaluation of the relationship between dose-volume histogram (DVH) parameters and RP in patients undergoing 3DCRT. Materials and Methods: DVHs of 41 lung cancer patients treated with 3DCRT were evaluated with respect to the development of grade ${\geq}2$ RP by excluding gross tumor volume (GTV) and planned target volume (PTV) from total (TL) and ipsilateral (IPSI) lung volume. Results: Were admitted statistically significant for p<0.05. Conclusions: The cut-off values for V5, V13, V20, V30, V45 and the mean dose of TL-GTV; and V13, V20,V30 and the mean dose of TL-PTV were statistically significant for the development of Grade ${\geq}2$ RP. No statistically significant results related to the development of Grade ${\geq}2$ RP were observed for the ipsilateral lung and the evaluation of PTV volume. A controlled and careful evaluation of the dose-volume histograms is important to assess Grade ${\geq}2$ RP development of the lung cancer patients treated with concurrent chemo-radiotherapy. In the light of the obtained data it can be said that RP development may be avoided by the proper analysis of the dose volume histograms and the application of optimal treatment plans.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.20
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• pp.8667-8671
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• 2014

Background: Survival rates after resection of advanced gastric cancer are extremely poor. An increasing number of patients with gastric carcinomas (GC) are therefore being treated with preoperative chemotherapy. We evaluated 36 month survival rate of GC patients that were treated by adding a neoadjuvant chemoradiotherapy before gastrostomy.Materials and Methods: Patients with stage II or III gastric adenocarcinomas were enrolled. The patients divided into two groups: (A) Neoadjuvant group that received concurrent chemoradiation before surgery (4500cGy of radiation at 180cGy per day plus chemotherapy with cisplatin and 5-fluorouracil, in the first and the end four days of radiotherapy). Resection was attempted 5 to 6 weeks after end of chemoradiotherapy. (B) Adjuvant group that received concurrent chemo-radiation after surgical resection. Results: Two (16.7%) patients out of 12 patients treated with neoadjuvant chemo-radiotherapy and 5 (38.5%) out of 13 in the surgery group survived after 36 months. These rates were not significantly different with per protocol and intention-to-treat analysis. The median survival time of patients in group A and B were 13.4 and 21.6 months, respectively, again not significantly different. Survival was significantly greater in patients with well differentiated adenocarcinoma in group B than in group A (p<0.004). Conclusions: According to this study we suggest surgery then chemoradiotherapy for patients with well differentiated gastric adenocarcinoma rather than other approaches. Additional studies with greater sample size and accurate matching relying on cancer molecular behavior are recommended.

• Radiation Oncology Journal
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• v.27 no.2
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• pp.71-77
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• 2009

Purpose: We investigated the outcome and the prognostic factors of patients with locally advanced esophageal cancer who were treated with concurrent chemo-radiotherapy. Materials and Methods: Two hundred forty six patients with esophageal cancer that were treated by radiotherapy between January 1994 and July 2007. Of these, 78 patients who received radiotherapy of $\geq$45 Gy with concurrent chemotherapy were retrospectively enrolled in this study. We included patients stages IIA, IIB, III, IVA, and IVB with supraclavicular metastasis in the middle/lower esophageal cancer or celiac node metastasis in cervical or upper/middle thoracic esophageal cancer. The median radiation dose was 54 Gy and the combination chemotherapy with 5-FU and cisplatin (FP chemotherapy) was given concurrently with radiotherapy in most patients (88%). Results: The follow-up period ranged from 2 to 117 months (median 14 months). The treatment response of the 54 patients could be evaluated by computerized tomography or endoscopy. A complete response (CR) was observed in 17 patients, whereas a partial response was observed in 18 patients. In patients with a CR, the median recurrence time was 20 months and the first relapse sites constituted a locoregional failure in 3 patients and a distant failure in 7 patients. The 1-, 2-, and 5-year overall survival (OS) rates were 58.9%, 21.7%, and 12.2%, respectively. The median survival period was 14 months. A univariate analysis indicated that the treatment response and cycles of FP chemotherapy were significant prognostic factors for OS. Daily or weekly administration of cisplatin as a radiosensitizer showed a better treatment response than FP chemotherapy. Conclusion: This study has shown that results of concurrent chemo-radiotherapy in patients with locally advanced esophageal cancer is comparable to those of other studies. Daily or weekly cisplatin administration may be considered as an alternative treatment in patients that are medically unfit for FP chemotherapy.

• Radiation Oncology Journal
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• v.19 no.2
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• pp.100-106
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• 2001

Purpose : We performed a retrospective analysis to compare short term results of induction chemotherapy-radiotherapy versus concurrent chemo-radiotherapy in patients with locally advanced nasopharyngeal carcinoma. Materials and Methods : From Oct. 1989 to May 1998, 62 patients with locally advanced nasopharyngeal carcinoma were treated with induction chemotherapy followed by radiotherapy (induction group) or concurrent chemo-radiotherapy (concurrent group). Induction chemotherapy was done for 50 patients, and concurrent chemotherapy for 12 patients. Age, sex, performance status, and pathologic types were evenly distributed between two groups. Stage distribution showed $32\%$ with IIB, $32\%$ with III, and $38\%$ with IV in induction group, and $50\%,\;33.3\%,\;and\;16.7\%$ in concurrent group, respectively. Chemotherapy regimen was CF (cisplatin and 5-FU) in both groups, and drug delivery method also same. Cisplatin $100\;mg/m^2$ was intravenously infused on day 1, and 5-FU $1,000\;mg/m^2$ on day $2\~6$. This was repeated at 3 weeks interval. At the end of radiotherapy, total cycles of chemotherapy were $1\~3$ (median 2) in both groups. Conventionally fractionated radiotherapy with daily fraction size $1.8\~2.0\;Gy$ and 5 fractions/week was done. Total dose was $69.4\~86\;Gy$(median 73.4 Gy) for induction group, and $69.4\~75.4\;Gy$ (median 70.8 Gy) for concurrent group. Follow-up time was $9\~116$ months (median 40.5 months) for induction group, $14\~29$ months (median 21 months) for concurrent group, respectively. Results : Overall 2 year survival rate (2YSR) for all patients was $78.7\%$. According to treatment modality, 2YSR were $77\%$ for induction group, $87\%$ for concurrent group (p>0.05). 2 year disease-free survival rate were $56\%$ and $81\%\;(p>0.05)$, respectively. Complete response to treatment were $75.5\%$ for induction group and $91.7\%$ for concurrent group, but there was no statistical difference. The incidence of grade $3\~4$ hematologic toxicity during radiotherapy was not differ between two groups, but grade 2 leukopenia was more frequent in concurrent group $(18\%\;vs\;66.7\%)$Grade $3\~4$ mucositis was more frequent in concurrent group $(4.0\%\;vs\;33.3\%)$. Overall incidence of grade $3\~4$ acute toxicity during radiotherapy was more frequent in concurrent group $(6.0\%\;vs\;41.7\%,\;p=0.005)$. Conclusion : Concurrent chemo-radiotherapy showed a trend of improvement in short-term survival and in treatment response when compared with induction chemotherapy-radiotherapy in locally advanced nasopharyngeal carcinoma. More controlled randomized trial are needed.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.11
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• pp.6883-6888
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• 2013

Background: Platinum based concurrent chemo-radiation is the de-facto standard of care in the non-surgical management of locally-advanced head and neck cancer of squamous origin. Three-weekly single agent cisplatin at 100 $mg/m^2$ concurrent with radical radiotherapy has demonstrated consistent improvement in loco-regional control and survival. This improvement is however at the cost of considerable hematologic toxicity and poor overall compliance. The routine use of this regime is improbable in developing countries with limited resources. We therefore aimed to determine the safety and efficacy of an alternative regime of weekly cisplatin and concurrent radiotherapy in such patients. Materials and Methods: January-05 and April-12, 188 patients of locally-advanced head and neck cancer of squamous origin were treated with concurrent weekly-cisplatin at $35mg/m^2$ and conventional radiotherapy 60-66Gy/30-33 fractions/5days per week. Results: Overall, 95% patients received planned doses of RT while 74% completed within the stipulated overall treatment time of <50 days. Eighty-two percent received at-least 5 weekly cycles. Grade-III/IV mucositis was seen in 58%/9% respectively, which resulted in mean weight loss of 9.2% from a pre-treatment mean of 54.5 kg. Grade-III hematologic toxicity-0.5%; grade II nephrotoxicity-2.5% and grade III emesis-3% were also seen. Grade-III/IV subcutaneous toxicity-10%/1% and grade-III/IV xerostomia-10%/0% were observed. Complete responses at the primary site, regional nodes and overall disease were seen in 86%, 89% and 83% patients respectively. The median and 5-years disease-free survival were 26 months and 39.4% respectively, while the median and overall survival were 27 months and 41.8% respectively. Conclusions: Weekly-cisplatin at 35 $mg/m^2$ when delivered concurrently with conventional radical RT (at-least 66y/33 fractions) in locally-advanced head and neck cancer is well tolerated with minimal hematologic and neprologic toxicity and can be routinely delivered on an out-patient basis. It is an effective alternative to the standard 3-weekly cisplatin especially in the context of developing countries.

• Radiation Oncology Journal
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• v.21 no.1
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• pp.54-65
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• 2003

Purpose : To analyze the gene expression Profiles of uterine ceulcal cancer, and its variation after radiation therapy, with or without concurrent chemotherapy, using a CDNA microarray. Materials and Methods :Sixteen patients, 8 with squamous ceil carcinomas of the uterine cervix, who were treated with radiation alone, and the other 8 treated w14h concurrent chemo-radiation, were Included in the study. Before the starling of the treatment, tumor biopsies were carried out, and the second time biopsies were peformed after a radiation dose of 16.2$\~$27 Gy. Three normal cervix tissues were used as a control group. The microarray experiments were peformed with 5 groups of the total RNAs extracted individually and then admixed as control, pre-radiation therapy alone, during-radiation therapy alone, pre-chemoradiation therapy, and during-chemoradlation therapy. The 33P-iabeled CDNAS were synthesized from the total RNAs of each group, by reverse transcription, and then they were hybridized to the CDNA microarray membrane. The gene expression of each microarrays was captured by the intensity of each spot produced by the radioactive isotopes. The pixels per spot were counted with an Arrayguage, and were exported to Microsoft Excel The data were normalized by the Z transformation, and the comparisons were peformed on the Z-ratio values calculated. Results : The expressions of 15 genes, including integrin linked kinase (ILK), CDC28 protein kinase 2, Spry 2, and ERK 3, were increased with the Z-ratio values of over 2.0 for the cervix cancer tissues compared to those for the normal controls. Those genes were involved In cell growth and proliferation, cell cycle control, or signal transduction. The expressions of the other 6 genes, Including G protein coupled receptor kinase 5, were decreased with the Z-ratio values of below -2.0. After the radiation thorapy, most of the genes, with a previously Increase expressions, represented the decreased expression profiles, and the genes, with the Z-ratio values of over 2.0, were cyclic nucleotlde gated channel and 3 Expressed sequence tags (EST). In the concurrent chemo-radiation group, the genes involved in cell growth and proliferation, cell cycle control, and signal transduction were shown to have increased expressions compared to the radiation therapy alone group. The expressions of genes involved in anglogenesis (angiopoietln-2), immune reactions (formyl peptide receptor-iike 1), and DNA repair (CAMP phosphodiesterase) were increased, however, the expression of gene involved In apoptosls (death associated protein kinase) was decreased. Conclusion : The different kinds of genes involved in the development and progression of cervical cancer were identified with the CDNA microarray, and the proposed theory is that the proliferation signal stalls with ILK, and is amplified with Spry 2 and MAPK signaling, and the cellular mitoses are Increased with the increased expression oi Cdc 2 and cell division kinases. After the radiation therapy, the expression profiles demonstrated 4he evidence of the decreased cancer cell proliferation. There was no sigificant difference in the morphological findings of cell death between the radiation therapy aione and the chemo-radiation groups In the second time biopsy specimen, however, the gene expression profiles were markedly different, and the mechanism at the molecular level needs further study.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.4
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• pp.1745-1754
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• 2016

Background: The prime output of Hospital Based Cancer Registries is stage and treatment based survival to evaluate patient care, but because of challenges of obtaining follow-up details a separate study on Patterns of Care and Survival for selected sites was initiated under the National Cancer Registry Programme of India. The results of stage and treatment based survival for head and neck cancers by individual organ sites are presented. Materials and Methods: A standardized Patient Information Form recorded the details and entered on-line at www.hbccrindia.org to a central repository - National Centre for Disease Informatics and Research. Cases from 12 institutions diagnosed between 1 January 2006 and 31 December 2008 comprised the study subjects. The patterns of treatment were examined for 14053 and survival for 4773 patients from five institutions who reported at least 70% follow-up as of 31 December 2012. Results: Surgical treatment with radiation for cancer tongue and mouth showed five year cumulative survival (FCS) of 67.5% and 60.4% respectively for locally advanced stage. Chemo-radiation compared to radiation alone showed better survival benefit of around 15% in both oro and hypo-pharyngeal cancers and their FCS was 40.0%; Hazard Ratio (HR):1.5;CI=1.2-1.9) and 38.7%; (HR):1.7; CI=1.3-2.2). Conclusions: The awareness about the requirement of concurrent chemo-radiation in specifically cancers of the oro and hypopharynx has to be promoted in developing countries. The annual (2014) estimate number of new Head and Neck cancers with locally advanced disease in India is around 140,000 and 91,000 (65%) patients do not receive the benefit of optimal treatment with ensuing poorer survival.