Identification of radiologic and clinicopathologic variables associated with tumor regression pattern and distribution of cancer cells after short-course radiotherapy and consolidation chemotherapy in patients with rectal cancer.

Background: Knowledge of the pattern of regression and distribution of residual tumor cells may assist in the selection of candidates for rectum-sparing strategies. Objective: To investigate and identify factors associated with tumor regression pattern and distribution of residual tumor cells. Methods: We conducted a prospective study of patients with T3/T4 N0/N+ adenocarcinoma of the middle and lower third of the rectum (≤10 cm) treated with radiotherapy (5×5 Gy) followed by 6 cycles of CAPOX chemotherapy. The pattern of tumor regression was classified as fragmented or solid. Microscopic intramural spread was measured. We used a model of distribution of residual tumor cells not yet applied to rectal cancer, defined as follows: type I (luminal), type II (invasive front), type III (concentric), and type IV (random). Results: Forty patients were included with a median age of 66 years; 23 (57.5%) were men. A fragmented pattern was identified in 18 patients (45.0%), and a solid pattern in 22 (55.0%). Microscopic intramural spread was identified in 25 patients (62.5%), extending from 1 to 18 mm (median, 4 mm). There were 14 cases (35.0%) of microscopic intramural spread ≥10 mm. All cases of fragmented regression pattern, except one, showed microscopic intramural spread. Within the fragmented pattern, microscopic intramural spread was 4-8 mm in 4 cases and ≥10 mm in the remaining cases. All cases of microscopic intramural spread ≥ 10 mm were within the fragmented pattern. Regarding the distribution pattern of residual tumor cells, 11 cases (31.5%) were classified as type I, 14 (40.0%) as type II, 10 (28.5%) as type III, and none as type IV. Carcinoembryonic antigen levels >5 ng/mL, downsizing <50%, residual mucosal abnormality >20 mm, and anatomopathologic lymph node involvement were significantly associated with the occurrence of fragmentation (P<0.05). Having received all 6 cycles of CAPOX chemotherapy and absence of microscopic intramural spread were significantly associated with the type I distribution pattern (P<0.05). Conclusion: The occurrence of a fragmented regression pattern is common, as is the presence of microscopic intramural spread. We could identify radiologic and clinicopathologic factors associated with the pattern of tumor regression and a type I distribution pattern.

miR-21 expression and clinical outcome in locally advanced pancreatic cancer: exploratory analysis of the pancreatic cancer Erbitux, radiotherapy and UFT (PERU) trial.

BACKGROUND: Locally advanced pancreatic cancer (LAPC) is associated with high mortality, and biomarker-driven treatment approach is currently lacking. This study evaluated safety and efficacy of a combination approach of chemotherapy followed by chemo-radiotherapy (CRT) +/- cetuximab, and the prognostic role of miR-21 in patients with LAPC treated with a multimodality approach. PATIENTS AND METHODS: This was a randomised phase II trial in which patients with inoperable LAPC were offered gemcitabine and capecitabine (GEM-CAP) for 16 weeks. Patients with stable disease or response after GEM-CAP were randomised to capecitabine or UFT plus radiotherapy (RT) (A), or capecitabine or UFT plus cetuximab plus RT (B). The primary outcome of the study was overall survival (OS). Clinical outcome was compared according to baseline circulating miR-21 levels. RESULTS: 17 patients were enrolled and treated with GEM-CAP, with 13 patients achieving disease control and being randomised to arms A (n:7) and B (n:6). After a median follow-up of 61.2 months, median progression free survival (PFS) was 10.4 months and 12.7 months, median OS was 15.8 months and 22.0 months in arms A and B respectively (p > 0.05). Patients with high baseline plasma miR-21 had worse PFS (3.5 vs. 12.7 months; p:0.032) and OS (5.1 vs 15.3 months; p:0.5) compared to patients with low miR-21. Circulating miR-21 levels reflected miR-21 expression within the tissues. CONCLUSIONS: Addition of Cetuximab to CRT following induction chemotherapy did not improve survival. High miR-21 baseline plasma expression was associated with poor clinical outcome in LAPC patients treated with induction chemotherapy followed by chemo-radiotherapy.

Concurrent chemo-radiotherapy in elderly patients: tolerance and compliance in a series of 137 patients.

INTRODUCTION: Aggressive cancer treatment is a challenge in elderly patients. The present study aims to assess tolerance in terms of acute toxicity and compliance of concurrent chemo-radiotherapy (cCRT) in a series of patients aged ≥70 years. MATERIALS AND METHODS: Clinical records of patients aged ≥70 years who underwent cCRT between January 2005 and December 2013 were reviewed. Concurrent CRT had curative intent in 134 patients (97.8 %) and palliative intent in 3 patients (2.2 %). Chemotherapy (CT) drugs and schedule were selected according to tumor histology. Radiotherapy median dose was 45.0 Gy (range 11-70 Gy) for curative purposes and 54 Gy (range 40-56 Gy) for palliative purposes. Incidence of acute toxicity and compliance to cCRT were analyzed and correlated with age, Karnofsky Performance Status (KPS), and Charlson Comorbidity Index (CCI). RESULTS: Overall, 137 patients, 82 males (60 %) and 55 females (40 %), median age 74 years (range 70-90 years) were analyzed. Concurrent CRT schedule was completed by 132 patients (96.4 %). Thirty-one of these patients (23.5 %) temporarily interrupted treatment. Hematological toxicity with grade ≥1 was observed in 25 patients (18.2 %), gastrointestinal toxicity in 55 (40.1 %), and genitourinary in 13 (9.5 %). Mucositis with grade ≥1 was recorded in 19 patients (13.9 %). No statistical significant correlation between KPS, CCI, and toxicity was found. A correlation trend between mucositis and patient age (p = 0.05) was observed. CONCLUSION: Concurrent CRT for elderly was feasible and quite well tolerated. Great attention in prescribing CT dose should be paid to limit acute toxicity.

Análisis retrospectivo institucional de tratamiento quimio-radioterápico definitivo en cáncer de cuello uterino localmente avanzado / Institutional retrospective analysis of definitive chemo-radiotherapy treatment in locally advanced cervical cancer

El objetivo fue analizar retrospectivamente, en pacientes con cáncer de cuello uterino localmente avanzado tratados en nuestro centro, el perfil de toxicidad de la radioterapia concurrente con platinos mono droga o combinados con gemcitabine y su impacto en el tratamiento. Estudio descriptivo, retrospectivo y observacional de pacientes con cáncer de cuello uterino localmente avanzado (estadios IIa/IVa) desde marzo de 2011 a febrero de 2016. Se analizaron características patológicas, dosis de tratamiento radiante y quimioterápico, así como toxicidades graves (GIII/IV) y su impacto en el tratamiento, observado como reducción o suspensión de dosis y/o split de radioterapia (RT). Se evaluaron 60 pacientes, edad mediana 47 años (17-75), 93% PS0-1. Histología: escamoso (89%) y adenocarcinoma (8%). Estadio IIb 24 (40%) y IIIb 16 (27%). Dosis de RT utilizada 5040cGy; 35 (58%) realizaron boost y 47 (78%) braquiterapia posterior. Cuarenta y cinco realizaron tratamiento concurrente con PLA y 15 con platinos/gemcitabine (PLA/GEM). En el grupo que recibió PLA, uno requirió reducción de dosis de quimioterapia (QT), dos suspendieron algún ciclo por toxicidad y tres realizaron split de RT. El 100% completó el tratamiento de quimioradioterapia (QRT) concurrente. En el grupo que recibió PLA/GEM: 9 requirieron reducción de dosis de QT, 11 suspendieron algún ciclo y 4 no completaron el esquema por toxicidad; 4 hicieron split de RT, y 87% completó el tratamiento de RT. En este estudio, el esquema concurrente con quimioterapia combinada muestra mayor toxicidad que impacta en el cumplimiento del tratamiento, 15% no lo completó por toxicidades graves. No obstante, un correcto manejo institucional de toxicidades, permite utilizar la combinación de tratamiento para obtener potenciales beneficios (AU)

This is a retrospective analysis of profile toxicity and treatment impact of gemcitabine plus platinum radiotherapy in patients with locally advanced cervix cancer, treated at our Centre. Descriptive, retrospective and observational study of patients with locally advanced cervix cancer (Ila/IVa stages), since March 2011 until February 2016. The analysis included the pathological characteristics, chemo radiotherapy doses, as well as severs toxicity (GIII/V) and it impact in treatment observed as reduction or suspension of doses and/or radiotherapy (RT) split. There were evaluated 60 patients of 47 median age (17-75), 93-5 PS0-1. Histology: 89% of squamous cell carcinoma and 8% of adenocarcinoma. 40% of IIb 24 and 27% of IIIB 16 stages. RT doses used 5040cGy; 35 pts (58%) did boost and 47 pts (78%) followed with brachytherapy. 45pts took PLA concurrent treatment, 15pts gemcitabine plus platinum (PLA/GEM). Regarding PLA group, one required a doses reduction of chemotherapy (QT), 2pts suspended a cycle due to toxicity and 3pts did RT split. 100% pts completed chemo radiotherapy (QRT) concurrent treatment. Regarding PLA/GEM group: 9pts required QT doses reduction, 11pts suspended a cycle due to toxicity and 4 didn´t complete the cycle due to toxicity; 4 did RT split and 87% completed RT. The study shown that the scheme of concurrent combined chemotherapy presents higher toxicity that impacts in the fulfillment of treatment, 66 ONCOLOGÍA CLÍNICA - Vol. 21 Nº 3 - Diciembre 2016 15% couldn´t complete due to sever toxicity. However, a correct institutional manage of toxicities allows to use treatment combination to obtain potential benefits (AU)

Evolving treatment strategies for colorectal cancer: a critical review of current therapeutic options.

Management of rectal cancer has markedly evolved over the last two decades. New technologies of staging have allowed a more precise definition of tumor extension. Refinements in surgical concepts and techniques have resulted in higher rates of sphincter preservation and better functional outcome for patients with this malignancy. Although, preoperative chemoradiotherapy followed by total mesorectal excision has become the standard of care for locally advanced tumors, many controversial matters in management of rectal cancer still need to be defined. These include the feasibility of a non-surgical approach after a favorable response to neoadjuvant therapy, the ideal margins of surgical resection for sphincter preservation and the adequacy of minimally invasive techniques of tumor resection. In this article, after an extensive search in PubMed and Embase databases, we critically review the current strategies and the most debatable matters in treatment of rectal cancer.

Valor pronóstico de la respuesta patológica a la radioquimioterapia preoperatoria en el cáncer de recto bajo localmente avanzado / Prognostic value of pathological response to chemo radiotherapy of locally advanced low rectal cancer

Background: preoperative chemo radiotherapy improves the prognosis of locally advanced low rectal cancer and induces a pathological response in the tumor, which may have prognostic value. Aim: to assess the results of rectal cancer treatment according to the degree of pathological response of the tumor after chemo radiotherapy. Patients and Methods: all patients with a locally advanced rectal cancer located within 11 cm of the rectal margin, subjected to preoperative chemo radiotherapy followed by surgical treatment in a period of 13 years, were included. Pathological response was classified as complete, intermediate and poor. The tumor was staged according to TNM 2002 classification. Survival was analyzed with Kaplan Meier curves and Cox regression. Results: patients were followed for a mean of 50 months (range 18-156). Exclusive and global local relapse was observed in 3 and 9.6 percent of patients, respectively. Pathological response was complete in 13 patients (none died), intermediate in 23 (three died) and poor in 68 (22 died). Global five years survival was 74 percent. There was a concordance of 0.64 between survival and pathological response. The concordance between survival and TNM classification was 0.69. Conclusions: the pathological response of the tumor to chemo radiotherapy has a good concordance with prognosis, although it is not superior to the final pathological status.

Introducción: la radioquimioterapia (RQT) preoperatoria en el manejo del cáncer de recto bajo localmente avanzado mejora el control locoregional y es capaz de inducir en el tumor una respuesta patológica (RP) variable que podría tener implicancia pronóstica. El objetivo de este estudio es evaluar el grado de RP inducida por la RQT y comparar los resultados oncológicos de acuerdo al grado de RP luego de RQT neoadyuvante. Pacientes y Método: se incluyen todos los pacientes con un tumor de recto localmente avanzado por debajo de los 11 cm al margen anal sometidos a RQT seguida de cirugía radical con intención curativa en un período de 13 años. La RP fue categorizada como completa, intermedia y pobre. Para la etapificación patológica se utilizó la clasificación TNM 2002. Las curvas de sobrevida fueron estimadas según Kaplan-Meier, se empleó el modelo de regresión de Cox para el análisis multivariado y los coeficientes de concordancia fueron evaluados según el estadístico C de Harrell y el K de Gonen-Heller. Resultados: seguimiento promedio 50 meses (extremos 18-156). La recidiva local exclusiva fue 3 por ciento y la recidiva local global fue 9,6 por ciento. La RP fue completa en 13 pacientes (no fallecidos), Intermedia (ypT1-T2N0) en 23 (3 fallecidos) y fue pobre (ypT3/T4 y/o LN+) en 68 (22 fallecidos). Sobrevida global a 5 años 74 por ciento. Hubo una fuerte correlación entre la sobrevida y la RP, con un coeficiente de concordancia (0,64) ligeramente inferior al coeficiente de la etapificación patológica definitiva de acuerdo al TNM (0,69). Conclusión: el grado de RP es un marcador que se correlaciona bien con el pronóstico oncológico con un índice de concordancia de 0,69 cuando se asocia con la localización del tumor, aunque no supera al estadio patológico final que alcanza un valor de 0,74.

Tratamiento concomitante con gemcitabina y radioterapia en pacientes con carcinoma epidermoide locorregionalmente avanzado de cabeza y cuello: estudio fase II / Concomitant treatment with gemcitabine and radiotherapy in patients with advanced stages of epidermoid carcinoma originating in the head and neck: a phase II sutdy

Antecedentes: En casos avanzados el tratamiento clásico del carcinoma epidermoide originado en mucosas de cabeza y cuello es cirugíaradioterapia o radioterapia sola (RTS). Sin embargo los resultados en carcinoma localmente avanzado (CLA) son decepcionantes. La asociación quimioterapia-radioterapia (QT-RT) ha demostrado ser superior a RTS en enfermedad irresecable y, en enfermedad resecable podría sustituir a la cirugía inicial y dejarla como rescate. Objetivo: El objetivo de este estudio es conocer la tasa de respuesta y la toxicidad del tratamiento concomitante Gemcitabina-Radioterapia (GRT) en pacientes con CLA. Material y métodos: Estudio prospectivo en el que pacientes con CLA recibieron GRT concomitante; se evaluó la tasa de respuesta global, completa, parcial y la toxicidad. Se incluyeron 15 pacientes, 5 mujeres y 10 hombres, 73% en etapa IVa. Resultados: Trece de 15 pacientes tuvieron respuesta global (87%), en 9(60%) fue completa (RC) y 2 tuvieron progresión. Todos tuvieron toxicidad, la más frecuente fue mucositis grado 4 en 46%; de éstos 40% requirió apoyo nutricio por sonda o gastrostomía. Un paciente en RC murió por sepsis. Ninguno abandonó el tratamiento. Conclusiones: La asociación GRT ofrece tasa de respuesta completa en 60%; sin embargo, la morbilidad no es despreciable; se requieren estudios aleatorizados con mayor número de pacientes que permitan definir el mejor esquema terapéutico.

BACKGROUND: Surgery, radiotherapy or radiotherapy alone (RTA) constitute conventional treatment regimes for advanced stages of squamous cell carcinoma originating in the head and neck mucosa. Nevertheless, the results in advanced regional carcinoma (ARC) are disappointing. The chemotherapy-radiotherapy (CHT-RT) association has shown to be superior to RTA in irresectable disease and in resectable disease it could substitute initial surgery as a rescue alternative. OBJECTIVE: Our objective is to report the response rate and toxicity of concurrent treatment with Gemcitabine and Radiotherapy (GRT) in patients with ARC. In a prospective design, patients with ARC received concurrent GRT; the global, complete and partial response rate as well as toxicity were assessed. MATERIAL AND METHODS: 15 patients were included, 5 women and 10 men, 73% in stage IVa; 13/15 showed a global response (87%), a complete response was observed in 9 cases (60%) (RC) and 2 showed progress. RESULTS: All patients included showed toxicity, the most frequent one was level 4 mucositis in 46%, of this 40% required nutritional support by catheter or gastrostomy. One patient in RC died due to sepsis. None of them suspended treatment. CONCLUSION: The GRT association offers a complete response rate of 60%; nevertheless morbidity was not insignificant; randomized studies with a larger number of patients will be required to allow us to outline the optimal therapeutic scheme.