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.

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.