A study on treatment of locally advanced squamous cell carcinoma of head and neck with radiation along with cisplatin or gefitinib

Background: Cisplatin based Concurrent chemo-radiation (CTRT) is the corner stone for treatment of locally advanced head and neck carcinoma. Epidermal growth factor receptor(EGFR) expression by squamous cell carcinoma which is associated with cancer development and progression,leads to emergence of anti-EGFR agents as a therapeutic option. In this study we compare cisplatin based CTRT against gefitinib based CTRT in terms of disease control and acute toxicity profile. Material and Methods: Stage III and IV squamous cell carcinoma of Head and neck region (excluding nasopharynx) were randomised into two groups. Control group received conventionally fractionated radiotherapy of 66Gy in 33fractions, over six and half weeks with concurrent weekly cisplatin. Study group received same dose of radiation with concurrent daily oral Gefitinib. All patients were followed up weekly during the treatment and then 6-8 weeks after completion of treatment and thereafter 3 monthly. Results: Overall response rate (complete response + partial response) was comparable for both arms (75% vs 76.2%, p value-0.881). Radiation with cisplatin was associated with significantly higher skin (28.6% vs 15%,p value-0.037) and mucosal (23.8% vs 5%,p-value-0.047) toxicities. Gefitinib containing arm showed significantly higher grade 3 diarrhoea (10% vs 0%, p-value-0.01) and skin rash (6% vs 0%, p -value-<0.001).With a median follow-up of 12.5 months Disease free survival (DFS) was not significantly different between the arms(12 vs 13 months). Conclusion: Gefitinib based CTRT is non-inferior to cisplatin based CTRT for the treatment of locally advanced head and neck carcinoma with acceptable toxicity profile.

Comparison of altered fractionation schedule with concurrent chemo-radiation for squamous cell carcinoma of head and neck

Background: Aim of the study was to compare the response of altered fractionation schedule with concurrent chemo-radiation in patients with primary and the nodal disease.Methods: Total of 40 patients (20 in each arm) with stage 1- 4 squamous cell carcinoma of the head and neck with a performance status of 0-2 (ECOG) were included in the study. Arm A was altered fractionation schedule where in patients received 6 fractions per week to a total dose of 6600 cGy in 33 fractions. In Arm B, patients received conventional radiotherapy with concurrent chemotherapy three weekly Inj. of cisplatin (100 mg/m2). Patients were evaluated for acute toxicity every week using the Acute Radiation Morbidity Scoring Criteria. The response was assessed after 6 weeks and 12 weeks post treatment using the RECIST criteria. Data was statistically analyzed.Results: Seventeen patients in Arm A and 18 patients in Arm B completed the treatment. At the end of three months, In Arm A, 7 patients had complete response and in Arm B, 9 patients had complete response of the primary (p>0.05).  When the complete nodal response was compared in both the arms, there was no difference (2 vs 4 in Arm A vs Arm B resp.). But there were more partial nodal responders in Arm B (p = 0.016). The acute toxicities were comparable in both the arms.Conclusions: Altered fraction radiotherapy can be used in early lesions with minimal nodal burden but with locally advanced disease or large nodal burden addition of chemotherapy should not be avoided.

A Study on the Outcome of Treatment among Patients with Hoarseness in a Tertiary Care Centre

Hoarseness is defined as the perceived rough, harsh or breathy quality of voice. Since both benign and malignant lesions can produce hoarseness, timely evaluation is very important because delay in the diagnosis of malignancy can adversely affect the outcome. We wanted to study the treatment and its outcome in patients with hoarseness of various aetiologies, and compare the response to treatment between various groups.METHODSThis was a longitudinal study conducted in the Department of ENT in a tertiary care centre in south India. In patients with hoarseness, history was elicited, clinical examination was done, and perceptual evaluation of voice was made using GRBAS (Grade, Roughness, Breathiness, Asthenia, Strain) scale. Direct laryngoscopy and biopsy were done whenever suspicious lesions were seen. Early laryngeal cancer was treated with radiotherapy, while advanced cases were treated with chemoradiation. Other cases were treated with medications, Video Laryngeal Surgery (VLS) or voice therapy, according to the diagnosis. Patients were kept under follow up; reassessment was done after six months regarding improvement/ persistence/ deterioration of previous symptoms. Laryngoscopy and perceptual evaluation of voice were repeated, and the data collected was analysed.RESULTSOn treatment, the lesion subsided completely, and hoarseness got relieved in all the cases of laryngitis, trauma, vocal nodule, vocal polyp and cyst, while the lesion subsided partially, and hoarseness improved in vocal cord palsy, papilloma and carcinoma of glottis. The response to treatment was better in benign lesions when compared to malignant lesions (P value < 0.0001) and better in glottic malignancies when compared to malignancies at other nearby sites (P value <0.001).CONCLUSIONSMost of the benign conditions that caused hoarseness subsided and voice became normal with medications, video laryngeal surgery and voice therapy, while hoarseness persisted to some extent after treatment with radiotherapy or chemoradiation in most of the patients with malignancy.

A prospective study comparing induction chemotherapy followed by chemoradiation versus chemoradiation alone in stage III non-small cell lung cancer

Background: Although concurrent chemoradiation (CCRT) is the standard of care for stage III non-small cell lung cancer(NSCLC), the five years overall (OS) survival is very poor. Most of the patients developed distant metastasis later which can be improved by induction chemotherapy. Aims: This study was designed to observe the difference in epidemiology, acute toxicities, overall responses [complete response (CR)+partial response (PR)] after treatment completion, disease-free survival (DFS) and progression-free survival (PFS) at the end of the study. Settings and Design: This was a prospective, interventional, randomized hospital-based study. Methods and Material: Eligible patients were randomized into arm A (CCRT with weekly paclitaxel(P) + Carboplatin(C) with 66 Gray radiation) and arm B (two cycles of induction chemotherapy consisted of P+C followed by CCRT as of arm A. During treatment weekly, after completion of treatment at 6th week and thereafter 3 monthly evaluation was done till the end of study. S tatistical analysis used: Chi-Square and Fisher Exact test did statistical analysis, t-test with 95%CI, Kaplan Meier survival analysis, Log Rank test using SPSS version 18. Results: Among 44 patients, male (88.6%), Smokers (85.1%) were predominant with the most common histology was squamous cell carcinoma (52.4%). Overall response (Complete Response +Partial Response) was higher in Arm B 66.66% but statistically non-significant. Acute toxicities in both the arms were comparable and similar. DFS and PFS in the induction chemotherapy arm (Arm B) were numerically superior to concurrent chemoradiation arm (Arm A) but statistically nonsignificant Conclusion: To conclude there were no significant differences in results between two arms in the present study population. Further studies with the larger sample size and longer duration of follow up are necessary.

Prospective study on radiation dose escalation in the treatment of squamous cell carcinoma of oesophagus with definitive concurrent chemo-radiation using three-dimensional conformal radiation therapy

Background: Poor local control and survival rates associated with radiation and chemotherapy in the management of locally advanced carcinoma of oesophagus have encouraged use of radiation dose escalation. This study analysed outcome and tolerance of radiation dose escalation with concurrent chemotherapy in non-metastatic squamous cell carcinoma of oesophagus. Materials and Methods: Patients diagnosed with stage I-III squamous cell carcinoma oesophagus, intended to be treated with radical chemo-radiation, between August 2015 to August 2017 were included in this prospective study. Baseline endoscopy, oral intake score and FACT E-QOL score were documented. Patients were treated with radiation dose of 60Gy in 2Gy per fraction schedule (initial 46Gy followed by 14Gy boost to tumour alone) with concurrent 3-weekly 5-FU/Cisplatin or weekly Cisplatin alone regimen. Results: Out of total of 20 eligible patients with median age of 64 years, majority had middle thoracic oesophageal tumour (60%), grade 2 dysphagia (75%) on oral intake scale. Patients with tumour length of ≤5cm (55%) or >5cm (45%) were categorised. Majority patients (85%) showed complete response at 3 months post treatment. The oral intake score and quality of life improved in 55% and 85%of the patients, respectively. Ten patients had disease progression with 40% of patients showing disease recurrence. No patient developed oesophageal fistula, radiation-pneumonitis or cardiac toxicity. Median disease-free survival and overall survival was 16 months (95% CI, 10-21 months) and 28 months (95% CI, 13-42 months) with 1-year and 2-year survival rates of 72.4% and 53.7%, respectively. Conclusion: Radiation dose escalation with concurrent chemotherapy in the management of stage I-III, non-metastatic squamous cell carcinoma oesophagus yields a good local control rate at 3 months with less severe complications and improved quality of life.

Salvage Concurrent Chemo-radiation Therapy for Loco-regional Recurrence Following Curative Surgery of Non-small Cell Lung Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: This study is to report clinical outcomes of salvage concurrent chemo-radiation therapy (CCRT) in treating patients with loco-regional recurrence (LRR) following initial complete resection of non-small cell lung cancer. MATERIALS AND METHODS: Between February 2004 and December 2016, 127 patients underwent salvage CCRT for LRR. The median radiation therapy (RT) dose was 66 Gy and clinical target volume was to cover recurrent lesion with margin without elective inclusion of regional lymphatics. Majority of patients (94.5%) received weekly platinum-based doublet chemotherapy during RT course. RESULTS: The median follow-up time from the start of CCRT was 25 months. The median survival duration was 49 months, and overall survival (OS) rates at 2 and 5 years were 72.9% and 43.9%. The 2- and 5-year rates of in-field failure-free survival, distant metastasis free survival, and progression free survival were 82.4% and 73.8%, 50.4% and 39.9%, and 34.6% and 22.3%, respectively. Grade ≥ 3 radiation-related esophagitis and pneumonitis occurred in 14 (11.0%) and six patients (4.7%), respectively. On both univariate and multivariate analysis, higher biologically equivalent dose (BED₁₀) (≥ 79.2 Gy₁₀ vs. 80 cm³; HR, 0.403), and longer disease-free interval (> 1 year vs. ≤ 1 year; HR, 0.489) were significantly favorable factors for OS. CONCLUSION: The current study has demonstrated that high dose salvage CCRT focused to the involved lesion only was highly effective and safe. In particular, higher BED₁₀, smaller CTV, and longer disease-free interval were favorable factors for improved survival.

Prospective study of radiation related adverse events and its management in cancer patient at tertiary care teaching hospital

Background: Radiation therapy is associated with certain adverse events which may cause significant discomfort to patient and may affect patient’s life. The objective of the study was to assess radiation related adverse events in the patients who are on radiation therapy and to prevent and manage these adverse events.Methods: A prospective observational study was conducted on 193 patients receiving radiotherapy in Oncology Department at Guru Gobind Singh Medical College and Hospital, Faridkot, Punjab. One fraction (2 Gray) dose had been given to patients daily for five days in a week and monitor. The collected data was analyzed by applying IBM SPSS v21.Results: The clinical results observed in 193 consecutive patients with follow-up of 7 weeks and graded according to RTOG Acute Radiation Morbidity Scoring Criteria. Majority of events were reported in age group of 41-60 years followed by 61-80 years, 20-40 years. Epidermal, mucosal, Genitourinary and Lower G.I. reactions are graded. The reactions managed by providing symptomatic treatment.Conclusions: Radiation related adverse events have been found frequently in patients with radiotherapy and chemo-radiotherapy both. As the number of doses increase with time the grade of reactions also increases. Appropriate follow-up and management of these events reduces patient burden of treatment.

Role of Neoadjuvant Chemotherapy followed by Concurrent Chemo-radiation in Locally Advanced Cervical Carcinoma: Our Experience

Background: Cervical carcinoma is the second most common cancer in females in India. Majority of them are reported in advanced stage. We have given platinum based neoadjuvant chemotherapy followed by CTRT in our study to reduce the local recurrence and decrease the tumor burden. The primary objective of our study was to assess the efficacy of NACT in terms of clinical and radiological response at the end of completion of treatment. Methods: This was a single arm prospective study in which we enrolled 79 patients from  2015-2017 who received 3 cycles of NACT, triweekly Cisplatin and 5-FU followed by concurrent chemo radiation (Radiotherapy-External beam radiotherapy 50Gy/25# plus intracavitary brachytherapy). Response was assessed at 12 weeks of completion of treatment by MRI pelvis using RECIST criteria 1.1 and toxicities were assessed weekly using CTCAE 4.03. Results: Mean age was 54 years; compliance rate was 88.6%. Complete response rate was 58.57% and partial response rate was 18.57% at 12 weeks post-treatment. Grade 2 or higher toxicities were seen in 52.85% patients during NACT and chemo radiation. Skin toxicities were seen in 37.14% followed by rectal-32.85%, haematological-27.14% and urinary bladder-24.28%. Conclusions: Neoadjuvant chemotherapy followed by Concurrent chemo radiation is a feasible treatment option with a good response rate with acceptable rate of treatment related toxicities.

Clinical effect of neoadjuvant chemo-radiation combined with thoracoscopic and laparoscopic three-incision esophagectomy / 中华消化外科杂志

Objective To explore the clinical effect of neoadjuvant chemo-radiation combined with thoracoscopic and laparoscopic three-incision esophagectomy for esophageal cancer.Methods The retrospective cohort study was conducted.The clinicopathological data of 111 esophageal cancer patients who underwent neoadjuvant chemo-radiation combined with thoracoscopic and laparoscopic three-incision esophagectomy in the Cancer Hospital of Chinese Academy of Medical Sciences between January 2010 and December 2016 were collected.Among 111 patients,68 with interval time between neoadjuvant chemo-radiation and thoracoscopic and laparoscopic three-incision esophagectomy ＜ 8 weeks were allocated into the ＜ 8 weeks group and 43 with interval time between neoadjuvant chemo-radiation and thoracoscopic and laparoscopic three-incision esophagectomy ≥8 weeks were allocated into the ≥8 weeks group.Patients underwent preoperative radiotherapy and chemotherapy with TP regimen,and then underwent selective thoracoscopic and laparoscopic three-incision esophagectomy.Observation indicators:(1) neoadjuvant chemo-radiation situations;(2) surgical and postoperative situations;(3) follow-up.Follow-up using outpatient examination and telephone interview was performed to detect postoperative survival of patients and tumor recurrence or metastasis up to March 2017.Measurement data with normal distribution were represented as (x)±s and comparison between groups was analyzed using the t test.Count data were analyzed using the chi-square test or Fisher exact probability.Comparison of ranked data was done by the nonparametric test.Results (1) Neoadjuvant chemo-radiation situations:all the patients underwent neoadjuvant chemo-radiation,without severe adverse reaction.Number of patients with complete remission based on oncopathology were 34 in the ＜8 weeks group and 15 in the ≥ 8 weeks group,with no statistically significant difference between the 2 groups (x2=2.441,P＞0.05).(2) Surgical and postoperative situations:all the patients underwent successful thoracoscopic and laparoscopic three-incision esophagectomy,with negative surgical margins.Operation time,volume of intraoperative blood loss,number of lymph node dissected,time of postoperative intrathoracic drainagetube removal,time of postoperative neck drainage-tube removal,hoarseness,upper gastrointestinal hemorrhage,anastomotic fistula,respiratory complication,pleural effusion and empyema,cardiovascular complication,incision abnormal healing,death within postoperative 30 days and duration of hospital stay were (354±103)minutes,(400± 76)mL,19±4,(11±4)days,(4.9±1.6)days,5,1,12,3,6,5,8,0,(19± 17) days in the ＜ 8 weeks group and (343±92) minutes,(392±51)mL,19±3,(12±6)days,(4.5±1.0)days,2,0,7,5,3,4,3,2,(18± 11) days in the ≥ 8 weeks group,respectively,with no statistically significant difference between the 2 groups (t =1.080,0.569,0.326,1.223,1.286,x2=0.029,0.035,1.114,0.000,0.000,0.246,t=0.315,P＞ 0.05).(3) Follow-up:90 of 111 patients were followed up for 3-82 months,with a median time of 25 months,including 55 in the ＜8 weeks group and 35 in the ≥8 weeks group.During follow-up,death and tumor recurrence were detected in 9,11 patients in the ＜8 weeks group and 6,11 patients in the ≥ 8 weeks group,respectively.Conclusion Neoadjuvant chemo-radiation combined with thoracoscopic and laparoscopic three-incision esophagectomy is safe and effective,and it doesn't increase the perioperative risks based on preoperative 8-week interval time.

Larynx Preservation Rate in Laryngeal Cancer Patients Treated with Chemotherapy and Radiotherapy: An Institutional Review of 250 Patients.

Introduction: Chemo-radiation preceded by induction chemotherapy is reported valuable alternative to laryngectomy in laryngeal cancer for larynx preservation.This study was performed to assess the influence chemo radiation on preservation of larynx. Materials and Methods: Two hundred and fifty sequential patients treated from January 2012 to December 2012 in our institute were reviewed and who were available for follow-up in this retrospective study. Total dose of 66-70 Gray was used at 2 gray per fraction daily for five days week were used. Larynx preservation rate at3 years of median follow-up were analyzed. Results: Among 250 patients, larynx preservation was possible in 170 patients (68%). With chemo-radiation, excellent preservation of larynx was achieved in stage II (78%) disease, while in advanced stage III and stage IVA, larynx preservation was67.06% and 64.35%, respectively. Conclusion: Chemo-radiation (either neoadjuvant chemotherapy followed by chemoradiation or concurrent chemo-radiation) has better larynx preservation rate in early as well was advanced laryngeal cancer patients.

Is neo‑adjuvant chemotherapy a better option for management of cervical cancer patients of rural India.

OBJECTIVES: To explore alternate modality of treatment in patients of advanced cancer cervix by neo‑adjuvant chemotherapy (NACT) followed by External Beam Radiotherapy (ERT) and Brachytherapy (BT). Short‑ (6 months) and long‑ (12 months) term follow‑up data from these patients were compared with the retrospective data from an urban cancer centre, where standard protocol of concurrent chemo‑radiotherapy is practiced. MATERIALS AND METHODS: Two hundred patients of advanced cervical cancer, treated at our rural cancer centre between January 2007 and December 2007, were included in the study arm (Group A). These patients received three cycles of neo‑adjuvant chemotherapy with Cisplatin, Bleomycin, and Vincristine before External‑Beam Radiotherapy (EBT) followed by brachytherapy. Patients in the control arm (Group B) of an urban cancer centre, received EBT with weekly concomitant Cisplatin, followed by brachytherapy. Short‑ (6 months) and long‑ (12 months) term follow‑up data from our patients were compared with the retrospective data from the urban cancer centre. RESULTS AND ANALYSIS: Complete response rate was comparatively higher among patients of Group A, also correspondingly proportion of patients showing progressive disease and stable disease was lower among them. Local treatment failure was 87.5% among patients from Group A and 94.4% in Group B patients. Concomitant chemoradiation (CRT) was associated with more GI toxicities. CONCLUSION: Our result suggests NACT arm is as effective as CRT arm in respect of complete response with less pelvic failure and G.I toxicities. Further follow‑up data are needed before arriving at a definite conclusion.

Comparison of acute toxicities and response of standard chemo radiation versus hyper fractionated radiotherapy in head and neck cancers

Background: Head and neck cancers are the most common malignancy among males in India. Carcinoma of buccal mucosa is the most common cancer among head and neck cancers due to high rate of tobacco chewing habit. Aim and objectives: To study the comparison of acute toxicities and response of standard chemo radiation versus hyper fractionated radiotherapy in head and neck cancers. Materials and methods: It was a prospective study of acute toxicity and response in patients diagnosed with head and neck malignancy. Patients with oral cavity site, previously untreated locally advanced III, IV-A and IV -B, age of 20-60 years. Results: Primary tumor site of the patients included in the both CRT arm and HFRT was not significant (P=0.755). Majority of patients included were T3 (44% in CRT arm and 46.7% in HFRT arm) and T2 (24% in CRT arm and 26.7% in HFRT arm) lesions. The tumors with respect to T stage, the difference between two arms was not statistically significant (P = 0.988). Most of the patients presented with N1 (44% of CRT arm and 40% of HFRT arm) and N2 (28% of CRT arm and 26.7% of HFRT arm) stage. With respect to nodal (N) stage at presentation, CRT arm and HFRT arm were comparable (P=0.987). In HFRT arm, 7 (46.7%) patients were presented in stage III Kuppa Prakash, A. Ravi Chandran, M. Vijay Kumar. Comparison of acute toxicities and response of standard chemo radiation versus hyper fractionated radiotherapy in head and neck cancers. IAIM, 2016; 3(9): 228-237. Page 229 and 8 (53.3%) patients were in stage IV. With respect to TNM stage, CRT arm and HFRT arm were comparable (P=0.87). Radiotherapy treatment compared in both CRT Arm and HFRT arms was not statistically significant (P=0.493). In CRT arm Grade 2 toxicity: 13/22 (59%) patients developed skin toxicity, 12/22 (55%) patients developed mucous membrane toxicity, 15/22 (68%) patients developed nausea, 8/22 (36%) patients developed vomiting, 10/22 (45%) salivary gland toxicity. Grade 3 toxicity: 2/22 (9%) patients developed skin toxicity, 10/22 (45%) patients developed mucous membrane toxicity, 5/22 (23%) patients developed nausea, 6/22 (27%) patients developed vomiting. Conclusion: Standard chemo radiation is better than HFRT in Head and Neck (oral cavity) cancers because of less toxicity, less mean overall treatment time, less number of treatment breaks and better response.

A 66 Patient Multi-Institution Phase IV Post-Authorization Surveillance of ProThelial™ (High Potency Polymerized Cross-linked Sucralfate) -Single Agent Efficacy for the Prevention and Rapid Reversal of Chemo-radiation Induced Oral, Esophageal and Intestinal Mucositis.

Background: Standard potency sucralfate is not recommended by most clinical guidelines for prevention or treatment of oral and intestinal mucositis. However, its polymerized cross-linked (thereby high potency) formulation (HPPCLS) was cleared by the FDA for management of oral mucositis and has been associated with complete prevention and rapid reversal of oral, esophageal and intestinal mucositis. Statistically significant high quality evidence from a 66 patient multi-institution phase IV non-controlled observation study is reported here. Patients and Methods: In February 2014, as part of the Phase IV post-approval surveillance of HPPCLS, a non-interventional mucositis registry was established. The primary aim of the registry was the surveillance of patients’ tolerance of HPPCLS. A secondary aim was the observation of the prescribing pattern of oncologists using HPPCLS to manage chemo-radiation induced mucositis. Inclusion Criteria: Any cancer treatment patient who developed or was anticipated to develop oral mucositis and was prescribed HPPCLS. Exclusion Criteria: Allergies or prior adverse reactions to sucralfate. Conduct of Study: Patients identified by oncology clinical staff with mucositis or anticipated to develop mucositis, were prescribed a 75 ml single week-supply of HPPCLS as needed. Results: Thirty-nine oncologists from 32 institutions prescribed HPPCLS to 66 patients. No adverse reactions were reported. Five patients were lost to follow-up and 61 patients reported outcomes. Eight patients experienced successful prevention of mucositis averting placement of gastrostomy tube and the remaining 53 patients with WHO-Grade 1-3 mucositis involving the mouth, esophagus, small bowel & colon experienced reversal in 2-3 days. Though cleared for oral use only, 48 of 61 patients were instructed by oncologists to swallow HPPCLS following swish-and-gargle. Statistical Analysis: Quantitative Glasziou rate-ratio treatment effect beyond 10 (37-82 for HPPCLS) supported efficacy (p≤0.05). Conclusion: HPPCLS paste may offer oncologists a single-agent approach to manage chemo-radiation induced mucositis. To wit a protocol is offered for practical use.

A comparison of results by sequential and concurrent chemo radiotherapy in locally advanced carcinoma esophagus.

Aim: Many Trials using sequential and concurrent chemo radiotherapy have been done so far and has established the role of concurrent chemo radiotherapy in treatment of inoperable carcinoma esophagus. In this study, we have compared the results of concurrent chemo radiotherapy with sequential chemo radiotherapy. We have treated inoperable carcinoma esophagus in both the settings and present here the comparison of results in the two settings. Materials and Methods: There were 26 patients of carcinoma esophagus in sequential and 31 in concurrent chemo radiotherapy arm. In sequential arm methotrexate and Cisplatin followed by radiotherapy was given whereas in concurrent arm, Cisplatin was given once weekly along with radiotherapy. Results: The 2 year survival was 38% in sequential and35.5% in the concurrent setting and the median survival was 19.5 and 18 months respectively in the two arms.The toxicities in both the arms were comparable. P value of 0.4774 with confidence interval of 95% was obtained, which is not significant. Dysphagia was improved earlier in sequential than in the concurrent arm. Conclusion: As the results and toxicities in both the arms are almost similar with better symptom control, so larger randomized trials are required to assess the response and the use of methotrexate in sequential chemo radiotherapy can be further explored.

Herpes Simplex Encephalitis Occurring During Chemo-Radiotherapy in Nasopharyngeal Carcinoma – A Case Report from Saudi Arabia.

Aim: To see possible association between the chemotherapy, radiotherapy or both with the reactivation of Herpes simplex virus 1(HSV1) in brain which merits further dialogue in the field of current evidence based literature. Presentation of Case: We present a case of 46 years old male patient who developed herpes simplex encephalitis (HSE) while receiving radical chemo-radiation for locally advanced nasopharyngeal carcinoma. Full informed consent was obtained for publication of this case. He was treated with protracted course of anti-virals and is currently leading a healthy life. Study Design: The study is a case report of a rare but important side effect of a common chemoradiation procedure. Place and Duration of Study: The study took place at Comprehensive Cancer Center, King Fahad Medical City. It was reported during June 2013. Discussion: HSV1 causes several disseminated primary infections including herpes labialis, gingivostomatitis, and corneal infections. It is particularly notorious for causing potentially fatal encephalitis. Its reactivation is linked to several environmental factors including chemotherapy and radiotherapy. Conclusion: This case report emphasizes on the possible role of chemo-radiation as causation of this life threatening condition, its early detection, prompt and aggressive treatment.

High Dose Involved Field Radiation Therapy as Salvage for Loco-Regional Recurrence of Non-Small Cell Lung Cancer

PURPOSE: To determine the effectiveness of salvage radiation therapy (RT) in patients with loco-regional recurrences (LRR) following initial complete resection of non-small cell lung cancer (NSCLC) and assess prognostic factors affecting survivals. MATERIALS AND METHODS: Between 1994 and 2007, 64 patients with LRR after surgery of NSCLC were treated with high dose RT alone (78.1%) or concurrent chemo-radiation therapy (CCRT, 21.9%) at Samsung Medical Center. Twenty-nine patients (45.3%) had local recurrence, 26 patients (40.6%) had regional recurrence and 9 patients (14.1%) had recurrence of both components. The median RT dose was 54 Gy (range, 44-66 Gy). The radiation target volume included the recurrent lesions only. RESULTS: The median follow-up time from the start of RT in survivors was 32.0 months. The rates of in-field failure free survival, intra-thoracic failure free survival and extra-thoracic failure free survival at 2 years were 52.3%, 33.9% and 59.4%, respectively. The median survival after RT was 18.5 months, and 2-year overall survival (OS) rate was 47.9%. On both univariate and multivariate analysis, the interval from surgery till recurrence and CCRT were significant prognostic factors for OS. CONCLUSION: The current study demonstrates that involved field salvage RT is effective for LRR of NSCLC following surgery.

Cáncer cérvico uterino estadio IIIB tratado con radioquimioterapia concomitante basada en cisplatino: experiencia inicial Hospital Carlos van Buren / Stage IIIB cervical cancer treated with concomitant cisplatin-based radiochemotherapy: initial experience Hospital Carlos van Buren

OBJETIVO: Analizar retrospectivamente resultados y factores pronósticos de pacientes con cáncer cérvico uterino estadío IIIB tratados con radio quimioterapia concomitante basado en cisplatino. MÉTODOS: Desde septiembre 1999 a diciembre 2002, 48 pacientes con cáncer cérvico uterino estadío IIIB fueron tratados en el Servicio de Oncología del Hospital Carlos Van Buren. La edad promedio fue 46,7 años. La histología correspondió a carcinoma escamocelular en 89,5% de los casos. El tratamiento consistió en radioterapia pelviana externa y braquiterapia útero-vaginal con baja tasa de dosis (dosis total de 85 Gy a punto A). La quimioterapia concomitante consistió en cisplatino semanal 40 mg/m² con máximo de 70 mg, por 5 semanas. RESULTADOS: 85,4% de las pacientes completó 5 ciclos de quimioterapia. La mediana de sobrevida global fue 39 meses, con una sobrevida global, sobrevida libre de enfermedad y sobrevida libre de recurrencia loco-regional a 3 años de 55,6%, 53,3% y 78,6%, respectivamente. 12,5% de los pacientes recidivó en pelvis y 22,9% desarrollaron metástasis a distancia. No se encontraron factores pronósticos de sobrevida global ni sobrevida libre de enfermedad, observando que diámetro tumoral clínico 7 cm y no realización de braquiterapia fueron factores de mal pronóstico de sobrevida libre de enfermedad loco-regional. CONCLUSIONES: El tratamiento con radioterapia pelviana externa, braquiterapia y quimioterapia concomitante con cisplatino semanal en pacientes con cáncer cérvico uterino estadío IIIB es posible de realizar en el sistema de salud público chileno, con buena tolerancia y resultados comparables a los de la literatura internacional.

OBJECTIVE: With a retrospective study we propose to analyze results and prognostic factors of patients with FIGO stage IIIB cervical carcinoma of the intact uterine cervix treated with cisplatin-based chemotherapy concurrently with standard radiotherapy. METHODS: From September 1999 to December 2002, 48 patients with stage IIIB cervical carcinoma were treated at the department of oncology from Carlos Van Buren Hospital. The mean age was 46.7 years; 89.5% was squamous cell carcinoma. Treatment consisted of radiotherapy (external-beam radiotherapy and low dose rate brachytherapy) plus weekly cisplatin chemotherapy (40 mg/m²) for five weeks. The total dose to point A was 85 Gy. RESULTS: 85.4% received 5 cycles. The median overall survival was 39 months with 3 year overall survival, disease-free survival and loco-regional disease-free survival of 55.6%, 53.3% and 78.6%, respectively. 12.5% had recurrence disease in pelvis and 22.9% developed metastatic disease. We did not find prognostic factors for overall survival and disease-free survival. Prognostic factors related with poor loco-regional disease-free survival were clinical tumor diameter 7 cm and patients who did not have brachytherapy. CONCLUSIONS: The treatment regimen of external pelvic irradiation, brachytherapy and concurrent weekly cisplatin in patients with stage IIIB cervical carcinomas is feasibility to do in the Chilean public health system, with good tolerance and comparable results to the international trials.

Gene Expression Profiles in Cervical Cancer with Radiation Therapy Alone and Chemo-radiation Therapy / 대한방사선종양학회지

PURPOSE: To analyze the gene expression profiles of uterine cervical cancer, and its variation after radiation therapy, with or without concurrent chemotherapy, using a cDNA microarray. MATERIALS AND METHODS: Sixteen patients, 8 with squamous cell carcinomas of the uterine cervix, who were treated with radiation alone, and the other 8 treated with concurrent chemo-radiation, were included in the study. Before the starting of the treatment, tumor biopsies were carried out, and the second time biopsies were performed after a radiation dose of 16.2~27 Gy. Three normal cervix tissues were used as a control group. The microarray experiments were performed 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-chemoradiation therapy. The 33P-labeled 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(R), and were exported to Microsoft Excel(R). The data were normalized by the Z transformation, and the comparisons were performed 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 6, were decreased with the Z-ratio values of below -2.0. After the radiation therapy, 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 nucleotide 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 angiogenesis (angiopoietin-2), immune reactions (formyl peptide receptor-like 1), and DNA repair (cAMP phosphodiesterase) were increased, however, the expression of gene involved in apoptosis (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 starts with ILK, and is amplified with Spry 2 and MAPK signaling, and the cellular mitoses are increased with the increased expression of Cdc 2 and cell division kinases. After the radiation therapy, the expression profiles demonstrated the evidence of the decreased cancer cell proliferation. There was no significant difference in the morphological findings of cell death between the radiation therapy alone 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.

Concurrent Chemo-Radiation Therapy for Advanced Hepatocellular Carcinoma with Portal Vein Thrombosis / 대한간학회지

BACKGROUND/AIMS: Advanced hepatocellular carcinoma with portal vein thrombosis has a poor prognosis. This study was undertaken to evaluate the therapeutic effects of concurrent chemo-radiation therapy in advanced hepatocellular carcinoma with portal vein thrombosis. METHODS: A total of 54 patients with advanced hepatocellular carcinoma (TNM stage IVa) were enrolled. Nineteen patients were treated with external beam radiotherapy (4,500 cGy/ 5 weeks) and intrahepatic arterial 5-FU infusion (500 mg on 1-5 day and 30-35 day, respectively) via implanted chemoport. The others were treated with intrahepatic arterial cisplatin infusion (80 mg/m2). RESULTS: In patients treated with concurrent chemo-radiation therapy, response rates at 2nd and 6th months were 42.1% and 26.3%, respectively. In patients treated with intrahepatic arterial cisplatin therapy, response rates at 2nd and 6th months were 2.9% and 0%, respectively. The median survival time was 11.6 months in concurrent chemo-radiation therapy and 4.8 months in intrahepatic arterial cisplatin infusion therapy. Concurrent chemo-radiation therapy produced better response rates and longer survival time than those of intrahepatic arterial cisplatin infusion therapy (p<0.05). CONCLUSIONS: Concurrent chemo-radiation therapy achieved favorable results in advanced hepatocellular carcinoma with portal vein thrombosis and can be considered as a treatment option for the management of advanced hepatocellular carcinoma.