Local treatment in oligometastasis from breast cancer: an overview

Oligometastasic breast cancer (OMBC) consists of breast cancer patient with a limited number of systemic metastases (≤ 5), all of them candidates for local ablative treatment with the intention of achieving long-term control of the metastasis and, eventually, an increase in survival The first consensus for the management of patients with oligometastatic breast cancer (OMBC) was published in 2007, establishing that a more aggressive multidisciplinary strategy is recommended in order to increase the survival while maintaining a good quality of life. The current scientific evidence is based on observational studies, mainly retrospective, systematic reviews and meta-analyses, and only a randomized nonexclusive study of oligometastatic (OM) published. All trials with Stereotactic Body Radiation Therapy (SBRT) in OM cancer have shown excellent tolerance and good local control, although first trials on Lung SBRT did not prove so excellent tolerance and had some deaths due to bronchus irradiation and secondary hemoptysis. There are multiple ongoing studies researching the benefit of SBRT in oligometastatic breast cancer. Despite the lack of impact on survival seen in the NRG BR-002 Trial, SBRT probably allows the delay of the systemic treatment until progression, and so, improves the quality of life of patients. We have to wait for the results of the ongoing and future studies for clarification of the role of local treatment in OMBC (AU)

[Paraneoplastic hemolytic anemia associated with prostate cancer. A case report].

Paraneoplastic syndromes are a group of tumor-related symptoms not directly attributable to tumors or metastasis. Symptoms are caused by secretion of substances by the tumor or the production of antibodies from immune cross-reactivity between tumor and normal tissues. Among hematological paraneoplastic syndromes, cancer-associated hemolytic anemias associated are rare, particularly in solid tumors. We present the case of a patient with localized bladder (high-grade infiltrating papillary carcinoma pT1) and prostate (Gleason 7) cancer who developed warm antibody autoimmune hemolytic anemia during radiation therapy for prostate cancer. It was resolved with prednisone (1 mg/Kg/day, tapering schedule). To the best of our knowledge, this is the first time an autoimmune hemolytic anemia is described in the literature as a paraneoplastic syndrome in such early stages of tumor disease.

Randomized Phase 2 Trial of a Novel Clonidine Mucoadhesive Buccal Tablet for the Amelioration of Oral Mucositis in Patients Treated With Concomitant Chemoradiation Therapy for Head and Neck Cancer.

PURPOSE: Oral mucositis (OM) is a frequent and painful sequela of concomitant chemoradiation (CRT) used for the treatment of head and neck cancer (HNC) for which there is no effective intervention. This randomized, placebo-controlled study evaluated the efficacy of a novel, mucoadhesive topical tablet formulation of clonidine in mitigating CRT-induced OM in patients with HNC. METHODS AND MATERIALS: Patients with HNC undergoing adjuvant radiation therapy (60-66 Gy; 5 × 1.8-2.2 Gy/wk) with concomitant platinum-based chemotherapy received daily local clonidine at 50 µg (n = 56), 100 µg (n = 65), or placebo (n = 62) via a topical mucobuccal tablet starting 1 to 3 days before and continuing during treatment. The primary endpoint was the incidence of severe OM (severe OM [SOM], World Health Organization grade 3/4). RESULTS: SOM developed in 45% versus 60% (P = .06) of patients treated with clonidine compared with placebo and occurred for the first time at 60 Gy as opposed to 48 Gy (median; hazard ratio, 0.75 [95% confidence interval, 0.484-1.175], P = .21); median time to onset was 45 versus 36 days. Opioid analgesic use, mean patient-reported mouth and throat soreness, and CRT compliance were not significantly different between treatment arms. Adverse events were reported in 90.8% versus 98.4%, nausea in 49.6% versus 71.0%, dysphagia in 32.8% versus 48.4%, and reversible hypotension in 6.7% versus 1.6% of patients on clonidine versus placebo, respectively. CONCLUSIONS: Although the primary endpoint was not met, the positive trends of OM-associated outcomes suggest that the novel mucoadhesive tablet delivery of clonidine might favorably affect the course and severity of CRT-induced SOM and support further evaluation.

Quality of life assessment by applying EORTC questionnaires to rectal cancer patients after surgery and neoadjuvant and adjuvant treatment.

BACKGROUND: Quality of Life (QoL) is a key element in rectal cancer (RC) patients. AIMS: this study assesses QoL in a sample of RC patients in their treatment follow-up period, and compares surgery modalities. PATIENTS AND METHODS: eighty four locally advanced RC patients who had received surgery and neoadjuvant chemoradiotherapy were included in the study. Of these, 70 had adjuvant chemotherapy. All patients completed the EORTC QLQ-C30 and the QLQ-CR29 once at least one year after completion of their treatment. Low anterior resection (LAR) patients also completed a Functional Evaluation questionnaire. RESULTS: QoL scores in the EORTC questionnaires for the sample as a whole were high in most dimensions, in line with the general population´s QoL values, although moderate limitations (> 30 points)were observed in urinary frequency, flatulence, impotence and sexual function. The scores for the Functional Evaluation were adequate (mean combined bowel function score of 18.2). LAR patients had a higher stool frequency than those with abdominoperineal resection (APR; p < 0.001). No differences in body image were found amongst LAR and APR patients. LAR patients with a lower anastomosis had higher faecal incontinence (p = 0.02), whereas those with a reservoir had better emotional functioning (p = 0.04) and higher faecal incontinence (p = 0.03). CONCLUSIONS: QoL scores and functional evaluation indicated patients had adapted to their disease and treatment. The few differences in QoL found between surgery modalities are in line with other recent studies and in contrast with earlier ones that suggested a lower QoL in APR patients.

Quality of life assessment by applying EORTC questionnaires to rectal cancer patients after surgery and neoadjuvant and adjuvant treatment

Background: Quality of Life (QoL) is a key element in rectal cancer (RC) patients. Aims: this study assesses QoL in a sample of RC patients in their treatment follow-up period, and compares surgery modalities. Patients and methods: eighty four locally advanced RC patients who had received surgery and neoadjuvant chemoradiotherapy were included in the study. Of these, 70 had adjuvant chemotherapy. All patients completed the EORTC QLQ-C30 and the QLQ-CR29 once at least one year after completion of their treatment. Low anterior resection (LAR) patients also completed a Functional Evaluation questionnaire. Results: QoL scores in the EORTC questionnaires for the sample as a whole were high in most dimensions, in line with the general population’s QoL values, although moderate limitations (> 30 points) were observed in urinary frequency, flatulence, impotence and sexual function. The scores for the Functional Evaluation were adequate (mean combined bowel function score of 18.2). LAR patients had a higher stool frequency than those with abdominoperineal resection (APR; p < 0.001). No differences in body image were found amongst LAR and APR patients. LAR patients with a lower anastomosis had higher faecal incontinence (p = 0.02), whereas those with a reservoir had better emotional functioning (p = 0.04) and higher faecal incontinence (p = 0.03). Conclusions: QoL scores and functional evaluation indicated patients had adapted to their disease and treatment. The few differences in QoL found between surgery modalities are in line with other recent studies and in contrast with earlier ones that suggested a lower QoL in APR patients (AU)

No disponible

Current management of gastric cancer.

Gastric cancer is a disease with high incidence and mortality in our population. The prognosis of patients with this disease is closely related to the neoplasm stage at diagnosis, including the following characteristics of the tumor: extension into the gastric wall thickness, spread to locoregional lymph nodes and the ability to generate distant metastases, as described by the TNM classification. For localized tumors characterized only by invasion of mucosa or submucosa at diagnosis, survival at 5 years is between 70 and 95% with exclusive surgical management; however, when extension into the gastric wall is higher and/or there is locoregional nodal involvement, survival decreases to 20-30% at 5 years. Currently, at high-volume centers, the extent of gastrectomy is individualized based on several parameters, which in an increasing number of cases allows a total gastrectomy with D2 lymphadenectomy and preservation of the spleen and pancreas. This improved procedure increases the chance of R0 surgery and improves the relationship between resected and affected lymph nodes, resulting in a decreased risk of the long-term locoregional recurrence. To improve these results, different therapeutic strategies combining chemotherapy or chemoradiotherapy with surgery have been tested. Previously, the Intergroup 0116 clinical trial, published in 2001, which changed clinical practice in the United States, showed that adjuvant chemoradiotherapy improved survival (from 26 to 37 months overall survival) of these patients. In Europe, perioperative chemotherapy has been considered the standard treatment, since the publication of two randomized phase III trials showed an increase at 5 years survival in the group treated with chemotherapy.

Situación actual en el tratamiento del cáncer gástrico / Current management of gastric cancer

El cáncer gástrico es un tumor de alta incidencia y mortalidad en nuestro medio, y su pronóstico está íntimamente relacionado con la situación neoplásica al diagnóstico, que incluye su extensión en el grosor de la pared gástrica, sobre los ganglios linfáticos locorregionales y su capacidad de generar metástasis a distancia, extensión basada en la clasificación TNM. En aquellos tumores localizados al diagnóstico, caracterizados por la invasión únicamente de mucosa-submucosa, la supervivencia a 5 años se establece entre el 70 y el 95% con manejo quirúrgico exclusivo, sin embargo, cuando la extensión en la pared es mayor y/o existe afectación ganglionar locorregional, la supervivencia disminuye al 20-30% a 5 años. Actualmente en centros con alto volumen de pacientes, la extensión de la gastrectomía se individualiza en función de varios parámetros, optándose, en cada vez más casos, por la realización de una gastrectomía total con linfadenectomía D2 y preservación esplenopancreática, pues esta aumenta las posibilidades de conseguir una cirugía R0 y mejora la relación entre ganglios resecados y ganglios afectados, lo que se traduce en una disminución del riesgo de recidiva locorregional a largo plazo. Con el objetivo de mejorar estos resultados, se han ensayado distintas estrategias terapéuticas de quimioterapia o quimiorradioterapia asociadas a la cirugía. Entre todas ellas destaca el ensayo 0116 del intergroup, publicado en el 2001, que cambió la práctica clínica asistencial en Estados Unidos, ya que demostró que un tratamiento de quimiorradioterapia tras la cirugía mejoraba la supervivencia (de 26 a 37 meses de mediana) de estos pacientes. En Europa es la quimioterapia perioperatoria el tratamiento estándar habitual, desde que se publicaron dos estudios aleatorizados fase III que demostraron un aumento en la supervivencia a 5 años en el grupo tratado con quimioterapia(AU)

Gastric cancer is a disease with high incidence and mortality in our population. The prognosis of patients with this disease is closely related to the neoplasm stage at diagnosis, including the following characteristics of the tumor: extension into the gastric wall thickness, spread to locoregional lymph nodes and the ability to generate distant metastases, as described by the TNM classification. For localized tumors characterized only by invasion of mucosa or submucosa at diagnosis, survival at 5 years is between 70 and 95% with exclusive surgical management; however, when extension into the gastric wall is higher and/or there is locoregional nodal involvement, survival decreases to 20-30% at 5 years. Currently, at high-volume centers, the extent of gastrectomy is individualized based on several parameters, which in an increasing number of cases allows a total gastrectomy with D2 lymphadenectomy and preservation of the spleen and pancreas. This improved procedure increases the chance of R0 surgery and improves the relationship between resected and affected lymph nodes, resulting in a decreased risk of the long- term locoregional recurrence. To improve these results, different therapeutic strategies combining chemotherapy or chemoradiotherapy with surgery have been tested. Previously, the Intergroup 0116 clinical trial, published in 2001, which changed clinical practice in the United States, showed that adjuvant chemoradiotherapy improved survival (from 26 to 37 months overall survival) of these patients. In Europe, perioperative chemotherapy has been considered the standard treatment, since the publication of two randomized phase III trials showed an increase at 5 years survival in the group treated with chemotherapy(AU)

The EORTC information questionnaire, EORTC QLQ-INFO25. Validation study for Spanish patients.

INTRODUCTION: The EORTC QLQ-INFO25 evaluates the information received by cancer patients. This study assesses the psychometric properties of the QLQ-INFO25 when applied to a sample of Spanish patients. MATERIALS AND METHODS: A total of 169 patients with different cancers and stages of disease completed the EORTC QLQINFO25, the EORTC QLQ-C30 and the information scales of the inpatient satisfaction module EORTC IN-PATSAT32 on two occasions during the patients' treatment and follow- up period. Psychometric evaluation of the structure, reliability, validity and responsiveness to changes was conducted. Patient acceptability was assessed with a debriefing questionnaire. RESULTS: Multi-trait scaling confirmed the 4 multi-item scales (information about disease, medical tests, treatment and other services) and eight single items. All items met the standards for convergent validity and all except one met the standards of item discriminant validity. Internal consistency for all scales (α>0.70) and the whole questionnaire (α>0.90) was adequate in the three measurements, except information about the disease (0.67) and other services (0.68) in the first measurement, as was test-retest reliability (intraclass correlations >0.70). Correlations with related areas of IN-PATSAT32 (r>0.40) supported convergent validity. Divergent validity was confirmed through low correlations with EORTC QLQ-C30 scales (r<0.30). The EORTC QLQ-INFO-25 discriminated among groups based on gender, age, education, levels of anxiety and depression, treatment line, wish for information and satisfaction. One scale and an item showed changes over time. CONCLUSIONS: The EORTC QLQ-INFO 25 is a reliable and valid instrument when applied to a sample of Spanish cancer patients. These results are in line with those of the EORTC validation study.

The EORTC Quality of Life questionnaire for patients with colorectal cancer: EORTC QLQ-CR29 validation study for Spanish patients.

INTRODUCTION: The EORTC Quality of Life (QL) Group has developed a questionnaire -the EORTC QLQ-CR29- for evaluating QL in colorectal cancer. The aim of this study is to assess the psychometric properties of the EORTC QLQCR29 when applied to a sample of Spanish patients. MATERIALS AND METHODS: Eighty-four locally advanced rectal cancer patients in the treatment follow-up period after receiving surgery and neoadjuvant chemoradiotherapy were included in the study. Seventy subjects also had adjuvant chemotherapy. Patients completed both the EORTC QLQC30 and the QLQ-CR29 once. The psychometric evaluation of the questionnaire's structure, reliability, and convergent, divergent and known-groups validity was performed. RESULTS: Multitrait scaling analysis showed that three of the multi-item scales met the standards of convergent and discriminant validity. These same scales reached the 0.7 Cronbach's coefficient criterion or were close to it. In both analyses exceptions were observed in the blood and mucus in stool scale. Correlations between the scales of the QLQC30 and the module were low (r<0.02) in most cases. A few areas with more related content had higher correlations (r<0.05). Group comparison analyses showed differences in QL between groups of patients based on age, comorbidity, performance status, receipt of adjuvant chemotherapy and surgery modality. CONCLUSIONS: The EORTC QLQ-CR29 is a reliable and valid instrument when applied to a sample of Spanish rectal cancer patients. These results are in line with those of the EORTC validation study.

Soporte con nutrición enteral en tumores de cabeza y cuello / No disponible

No disponible

The eortc quality of life questionnaire QLQ-C30 (version 3.0). Validation study for Spanish prostate cancer patients.

OBJECTIVE: The EORTC Quality of Life Group has developed a questionnaire for evaluating Quality of Life in international clinical trials: EORTC QLQ-C30, which is widely used in many countries. The purpose of this study was to assess the psychometric properties of the third version of this questionnaire, EORTC QLQ-C30 (version 3.0), when applied to Spanish prostate cancer patients. METHODS: A sample of 137 prostate cancer patients prospectively filled in the questionnaire three times: on the first and last day of the treatment, and in the followup period. Psychometric evaluation of the structure, reliability and validity was made. RESULTS: Multitrait scaling analysis showed that most item-scale correlation coefficients met the standards of convergent and discriminant validity. Few exceptions appeared mainly in CF Most scales had low to moderate inter-correlations. Cronbach's coefficients of the scales were above 0.7, except for the CF and NV values. Group comparison analyses showed better QL in patients with higher Performance Status. Changes in functioning and symptom areas appeared throughout the different measurements, which were in line with the treatment process. CONCLUSIONS: The EORTC QLQC30 (version 3.0) appeared as a reliable and valid instrument when applied to a sample of Spanish prostrate cancer patients. The results are in line with previous studies.

The EORTC Quality of life questionnaire OLO-C30 (version 3.0). Validation study for Spanish prostate cancer patients / Cuestionario de calidad de vida QLQ-C30 (versión 3.0): Estudio de validación en español con pacientes con cáncer de próstata

Objective: The EORTC Quality of Life Group has developed a questionnaire for evaluating Quality of Life in international clinical trials: EORTC QLQ-C30, which is widely used in many countries. The purpose of this study was to assess the psychometric properties of the third version of this questionnaire, EORTC QLQ-C30 (version 3.0), when applied to Spanish prostate cancer patients. Methods: A sample of 137 prostate cancer patients prospectively filled in the questionnaire three times: on the first and last day of the treatment, and in the follow-up period. Psychometric evaluation of the structure, reliability and validity was made. Results: Multitrait scaling analysis showed that most item-scale correlation coefficients met the standards of convergent and discriminant validity. Few exceptions appeared mainly in CF. Most scales had low to moderate inter-correlations. Cronbach's coefficients of the scales were above 0.7, except for the CF and NV values. Group comparison analyses showed better QL in patients with higher Performance Status. Changes in functioning and symptom areas appeared throughout the different measurements, which were in line with the treatment process. Conclusions: The EORTC QLQ-C30 (version 3.0) appeared as a reliable and valid instrument when applied to a sample of Spanish prostrate cancer patients. The results are in line with previous studies (AU)

Objetivo: El Grupo de Calidad de Vida de la EORTC ha desarrollado un cuestionario para evaluar la Calidad de Vida en ensayos clínicos internacionales: EORTC QLQ-C30, el cual es ampliamente utilizado en muchos países. El objetivo de este trabajo es evaluar las propiedades psicométricas de la tercera versión de este cuestionario, EORTC QLQ-C30 (versión 3.0), al ser administrado a pacientes españoles con cáncer de próstata. Métodos: Una muestra de 137 pacientes con cáncer de próstata han contestado el cuestionario de forma prospectiva tres veces: el primer y último día de tratamiento, y durante el período de seguimiento. Se ha realizado una evaluación psicométrica de su estructura, fiabilidad y validez. Resultados: los análisis multirasgo-multimétodo han mostrado que la mayoría de las correlaciones ítem-escala satisfacían los criterios de validez convergente y divergente. Se han dado pocas excepciones, principalmente en la escala CF. La mayoría de las correlaciones entre escalas eran bajas o moderadas. Los coeficientes Alpha de Cronbach de las escalas eran superiores a 0,7, excepto en las escalas CF y NV. Los análisis de comparación entre grupos han indicado que se da una mejor Calidad de Vida en pacientes con mayor performance status. Se han dado cambios en áreas de funcionamiento y de síntomas a lo largo de las diferentes medidas, que han ido en línea con el proceso de tratamiento. Conclusiones: el EORTC QLQ-C30 (versión 3.0) se ha mostrado como un instrumento fiable y válido al ser aplicado a una muestra de pacientes españoles con cáncer de próstata. Los resultados van en línea con los estudios de validación previos (AU)

Quality of Life assessment through the EORTC questionnaires of colorectal cancer patients in advanced disease stages.

PURPOSE: The purpose of the present work is to evaluate Quality of Life in a group of colorectal cancer patients in advanced stages of their disease, along a standard chemotherapy treatment protocol, through the EORTC core questionnaire QLQ-C30 and the colorectal cancer module QLQ-CR38. These two questionnaires had previously been validated in our country. The present study has the novelty of its use during the chemotherapy treatment. MATERIALS AND METHODS: A consecutive sample of 44 colon o rectal cancer patients in stage IV, from an initial group of 46 patients who were addressed, have filled in the questionnaires, in three moments during their treatment process. Clinical and demographic data have also been recorded. Quality of Life scores and changes in them among the three assessments have been calculated. RESULTS: The quality of life scores of patients who have followed the treatment have been >70 points (100) in most dimensions, and has shown similar to the clinical data. Changes of >20 points in the quality of life scores during the treatment process appear in areas related to toxicity, fatigue and insomnia. Quality of life has been stable or has had small changes (between 10 and 20 points) in most dimensions. CONCLUSIONS: Quality of Life in the present sample has been good in general. The treatment has been administered to patients who could tolerate it adequately.

Quality of Life assessment through the EORTC questionnaires of locally advanced rectal cancer patients treated with preoperative chemo-radiotherapy.

PURPOSE: To assess the quality of life in a group of rectal cancer patients during the treatment period. MATERIAL AND METHODS: A sample of 83 rectal cancer patients in Dukes' stages B2 or C who started a chemoradiotherapy treatment followed by surgery, have filled in the EORTC core questionnaire QLQC30 and the colorectal module QLQ-CR38, in three moments during the treatment and follow-up periods: at the beginning of the treatment, at the end of the chemoradiotherapy, and after surgery. Clinical and demographic data have also been recorded. Quality of Life scores and changes in them among the three assessments have been calculated. RESULTS: Quality of life scores of patients who have followed the treatment has been good in most dimensions, and has shown similar to the clinical data. Soft and moderate alterations have appeared in the areas of disease symptoms, treatment toxicity, fatigue, emotional and sexual functioning, and also in functional areas after surgery. Quality of life has been stable or has had small changes in most dimensions. A worsening in toxicity areas has appeared after the neoadyuvant treatment. After surgery there has been a worsening in functional areas, fatigue and appetite loss, and an improvement in diarrhoea. CONCLUSIONS: Quality of life scores and clinical data indicate that the situation of the patients who have received the treatments has been good. Patients under treatment stood it adequately.

Quality of Life assessment through the EORTC questionnaires of locally advanced rectal cancer patients treated with preoperative chemo-radiotherapy

No disponible

Purpose. To assess the quality of life in a group ofrectal cancer patients during the treatment period.Material and methods. A sample of 83 rectal cancerpatients in Dukes’ stages B2 or C who started achemoradiotherapy treatment followed by surgery,have filled in the EORTC core questionnaire QLQC30and the colorectal module QLQ-CR38, in threemoments during the treatment and follow-up periods:at the beginning of the treatment, at the end ofthe chemoradiotherapy, and after surgery. Clinicaland demographic data have also been recorded.Quality of Life scores and changes in them amongthe three assessments have been calculated.Results. Quality of life scores of patients who havefollowed the treatment has been good in most dimensions,and has shown similar to the clinical data.Soft and moderate alterations have appeared inthe areas of disease symptoms, treatment toxicity,fatigue, emotional and sexual functioning, and alsoin functional areas after surgery. Quality of life hasbeen stable or has had small changes in most dimensions.A worsening in toxicity areas has appeared afterthe neoadyuvant treatment. After surgery there hasbeen a worsening in functional areas, fatigue andappetite loss, and an improvement in diarrhoea.Conclusions. Quality of life scores and clinical dataindicate that the situation of the patients who havereceived the treatments has been good. Patients undertreatment stood it adequately

Quality of life in patients with locally advanced head and neck cancer treated with chemoradiotherapy. Comparison of two protocols using the EORTC questionnaires (QLQ-C30, H and N35).

INTRODUCTION: The objective of this study is to assess the quality of life (QoL) of two groups of patients during treatment for locally advanced head and neck (H and N) cancer. MATERIAL AND METHODS: Two samples of 30 patients each in AJCC stages III and IV undergoing either of two chemo-radiotherapy protocols completed the EORTC QLQ-C30 general questionnaire and the QLQ-H and N35 H and N module on three occasions during the treatment and follow-up periods. We also collected clinical data. The QoL scores and their evolution over the three measurements were calculated and both protocols were compared during the treatment period. RESULTS: The QoL scores are acceptable in general. Limitations were observed in relation to toxicity, psycho-social and some functional areas during the treatment. QoL improved in the follow-up period. The clinical and QoL data are better in one of the two treatment protocols. DISCUSSION: The QoL scores indicate that the condition of the patients receiving the protocols was acceptable, considering the severity of their disease. The treatments were reasonably-well tolerated.

Quality of life in patients with locally advanced head and neck cancer treated with chemoradiotherapy. Comparison of two protocols using the EORTC questionnaires (QLQ-C30, H&N35)

Introduction. The objective of this study is to assess the quality of life (QoL) of two groups of patients during treatment for locally advanced head and neck (H&N) cancer. Material and methods. Two samples of 30 patients each in AJCC stages III and IV undergoing either of two chemo-radiotherapy protocols completed the EORTC QLQ-C30 general questionnaire and the QLQ-H&N35 H&N module on three occasions during the treatment and follow-up periods. We also collected clinical data. The QoL scores and their evolution over the three measurements were calculated and both protocols were compared during the treatment period. Results. The QoL scores are acceptable in general. Limitations were observed in relation to toxicity, psycho-social and some functional areas during the treatment. QoL improved in the follow-up period. The clinical and QoL data are better in one of the two treatment protocols. Discussion. The QoL scores indicate that the condition of the patients receiving the protocols was acceptable, considering the severity of their disease. The treatments were reasonably-well tolerated