Israel Medical Association Journal

Background: Stereotactic ablative radiation therapy (SABR) is the application of a very high radiation dose to a small treatment volume. It is the new standard of care in medically inoperable early-stage lung cancer. 

Objectives: To report the outcomes of SABR in stage I lung cancer at Sheba Medical Center since its introduction in 2009.

Methods: We conducted a retrospective chart review of patients with stage I lung cancer treated during the period 2009–2015. Survival status was retrieved from the electronic medical records and confirmed with the national registry. Local failure was defined as increased FDG uptake on PETCT scan within a 2 cm radius of the treated region. Toxicity was estimated from medical records and graded according to common toxicity criteria for adverse events (CTCAE) version 4.03. Overall survival and local control were estimated by the Kaplan-Meier method.

Results: During the study period 114 patients were treated for 122 stage I lung cancer lesions. Median follow-up time was 27 months (range 8.2–69.5 months), median age was 76 years. Eighty-two percent of the tumors were stage IA (size ≤ 3 cm). Median survival was 46 months; estimated 3 year overall survival was 59% (95%CI 47–69%) and local control was 88% (95%CI 78–94%). Toxicity included chest wall pain in 8.4% of patients, rib fracture in 0.9%, grade 1–2 pneumonitis in 12%, grade 3 in 12% and grade 5 (death) in 0.9%.

Conclusions: SABR has been successfully implemented at Sheba Medical Center for the treatment of stage I lung cancer in inoperable patients. It is associated with excellent local control, minor toxicity and an acceptable overall survival.

 

Background: Antibiotic treatment of Clostridium difficile infection (CDI) has a high failure rate. Fecal microbiota transplantation (FMT) has proven very effective in treating these recurrences. 

Objectives: To determine which method of fecal microbiota transplantation (upper or lower gastrointestinal) and which type of donor (a relative or unrelated) is superior.

Methods: This is a retrospective analysis of treatment protocols and outcomes in 22 patients with refractory or recurrent CDI who underwent FMT at two Israeli facilities. Each center used a different donor type, stool preparation and method of delivery. The Tel Aviv Sourasky Medical Center used unrelated fecal donors and frozen stool samples and delivered them primarily (92%) via the lower gastrointestinal (GI) tract. Shaare Zedek Medical Center used fresh donor stool of relatives and delivered them primarily (90%) via the upper GI tract.

Results: FMT had an overall 2 month cure rate of 89%. Patients treated with FMT that was executed through the lower GI tract recovered faster from the infection (1.6 ± 1.08 vs. 2.4 ± 1 days for the upper tract, P = 0.03). The results also showed that patients who received lower GI tract FMTs were more likely to be cured of CDI (100% vs. 75% for upper tract FMTs, P = 0.16). Five patients (22%) died of CDI/FMT-unrelated causes and two (10%) died of CDI/FMT-related causes during the study period.

Conclusions: Lower GI tract FMT is a safe and effective treatment for refractory and recurrent CDI, and yields quicker results than upper GI tract FMT. 

 

Background: The effects of balneotherapy on rheumatoid arthritis (RA) are still controversial partly due to poor methodology used in randomized controlled trials, as reported in the international medical literature. 

Objectives: To determine whether spa therapy plus pharmacological treatment offers any benefit in the management of RA as compared to pharmacological treatment alone.

Methods: We conducted a prospective, controlled, unblinded randomly assigned study of patients with RA according to American College of Rheumatology criteria. Following the 2007 recommendations of AFRETH, the method designed for this study was “immediate treatment versus delayed treatment.” All patients were followed at the Centro Hospitalar do Porto and each physician observed the same patients throughout the study. Patients continued with their usual medications and maintained their daily life activities at home, at leisure and/or in the workplace. The spa therapy group received spa treatments for 21 days at S. Jorge Spa-Santa Maria da Feira. The main outcome measure was the HAQ-DI; the moderated regression analysis, together with the Johnson-Neyman technique, was used for statistical analysis.

Results: HAQ-DI at the end of treatment (21 days) and at the 3 month follow-up was improved in the spa group (odds ratio 0.37, confidence interval 0.09–0.64, P = 0.01 at 21 days, and 0.44, 0.15–0.72, P = 0.004 at 3 months).

Conclusions:

Long-term extension studies and observational drug registers have revealed an increased risk of serious infections in patients treated with anti-tumor necrosis factor agents, particularly infliximab, etanercept and adalimumab. The same may be true for the newer biological drugs rituximab, tocilizumab and abatacept, although this has yet to be confirmed by long-term observational studies. We review the risk of tuberculosis, herpes zoster and other opportunistic infections, and the recommendations for screening for tuberculosis and hepatitis B and C infections in patients affected by rheumatoid arthritis, with the aim of informing patients and encouraging greater awareness among physicians.

Background: Radiation-induced dermatitis is commonly seen during radiotherapy for breast cancer. Melatonin-based creams have shown a protective effect against ultraviolet-induced erythema and a radioprotective effect in rats.

Objectives: To evaluate the efficacy of melatonin-containing cream in minimizing acute radiation dermatitis. 

Methods: In this phase II, prospective, randomized, placebo-controlled double-blind study, patients who underwent breast-conserving surgery for stage 0-2 breast cancer were randomly allocated to melatonin emulsion (26 women) or placebo (21 women) for twice daily use during radiation treatment and 2 weeks following the end of radiotherapy. All women received 50 Gy whole breast radiation therapy with 2 Gy/fx using computed tomography-based 3D planning. Patients were examined and completed a detailed questionnaire weekly and 2 weeks following the end of treatment.

Results: The occurrence of grade 1/2 acute radiation dermatitis was significantly lower (59% vs. 90%, P = 0.038) in the melatonin group. Women older than 50 had significantly less dermatitis than younger patients (56% vs. 100%, P = 0.021). The maximal radiation dermatitis in the study group was grade 2 in 15% of the treated patients.

Conclusions: Patients treated with melatonin-containing emulsion experienced significantly reduced radiation dermatitis compared to patients receiving placebo.

Background: Balneotherapy is one of the most commonly used non-pharmacological approaches for osteoarthritis (OA). Recent data indicate that some biomarkers could be useful to predict OA progression and to assess therapeutic response.

Objectives: To evaluate the effects of mud-bath therapy on serum biomarkers in patients with knee OA. 

Methods: The study group comprised 103 patients with primary symptomatic bilateral knee OA who were randomly assigned to receive a cycle of mud-bath therapy over a period of 2 weeks or to continue their standard therapy alone. Clinical and biochemical parameters were assessed at baseline and after 2 weeks. Clinical assessments included global pain score on a Visual Analogue Scale (VAS) and the Western Ontario and McMaster Universities Index (WOMAC) subscores for knee OA. Cartilage oligomeric matrix protein (COMP), C-terminal cross-linked telopeptide type II collagen (CTX-II), myeloperoxidase (MPO) and high sensitivity C-reactive protein (hsCRP) serum levels were assessed by ELISA.

Results: At the end of mud-bath therapy we observed a statistically significant improvement in VAS and WOMAC subscores. Serum levels of COMP, MPO and hsCRP did not show any significant modification in both groups, while a significant increase (P < 0.001) in CTX-II serum levels was observed in the mud-bath group after the treatment.

Conclusions: A cycle of mud-bath therapy added to usual treatment had a beneficial effect on pain and function in patients with knee OA. The evaluation of serum biomarkers showed only a significant increase of CTX-II, perhaps due to an increase of cartilage turnover induced by thermal stress.

Background: Androgen deprivation therapy (ADT) added to radiation therapy (RT) in intermediate to high risk prostate cancer negatively impacts quality of life. 

Objectives: To compare health-related quality of life (HR-QOL) in patients receiving combined RT with and without ADT 

Methods: The study population comprised patients treated with definitive RT for prostate cancer who completed the Expanded Prostate Cancer Index Composite-26 form between 3 and 24 months after completing RT. Covariance and a stepwise backward logistic regression model was used. 

Results: Data were available for 143 patients who received RT+ADT and 70 who received RT alone. The sexual function and hormonal vitality scores of patients receiving RT+ADT were significantly lower than those receiving RT alone (P < 0.0001). Patients with only compulsory school education had significantly lower sexual function scores than patients with university level education (P ≤ 0.005). Patients with depression had significantly lower hormonal vitality scores than those without depression (P ≤ 0.0001). 

Conclusions: The addition of ADT to RT is responsible for decrements in quality of life in the sexual and hormonal vitality domains, which is further compounded by lack of education and depression. This underlines the need to improve education, identify and treat depression, and develop strategies to improve the quality of life of patients receiving combination therapy. 

 

Background: Predictive biomarkers for personalized treatment of neoplasms are suggested to be a major advancement in oncology and are increasingly used in clinical practice, albeit based on level II evidence. Target Now® (TN) employs immunostaining and RNA expression on tumor samples to identify potentially beneficial or ineffective drugs. 

Objectives: To explore retrospectively the predictive value of TN for patients with colorectal and gastric carcinomas. 

Methods: The study group comprised colorectal and gastric carcinoma patients with TN test reports. We identified chemotherapy regimens given for stage IV disease for which TN reports indicated prediction. Protocols were classified as having clinical benefit (CB; i.e., stable disease or any objective response) or progressive disease, and this was compared with the TN prediction. 

Results: Nineteen patients – 12 colorectal and 7 gastric carcinomas – met the inclusion criteria. There were 26 evaluable treatment protocols; of 18 with a CB 15 were predicted to have a CB while 3 were predicted to have a lack of CB. Of eight protocols that had no CB, seven were predicted to have a CB and one was predicted to have a lack of CB. A chi-square test was non-significant (P = 0.78). An exploratory analysis yielded a positive predictive value of 68% and a sensitivity of 83% for the TN test. 

Conclusions: This study emphasizes the need for larger multicenter studies to validate the TN test before it is adopted into clinical practice. 

 

Background: Approximately 80% of patients with myelodysplastic syndromes (MDS) receive multiple red blood cells (RBC), often multiple transfusions, and are therefore prone to develop alloantibodies against RBC. Because of increasing evidence for the role of immune dysregulation in the pathobiology of MDS, we hypothesized that in patients with MDS there is an increase in alloantibody formation beyond that expected by multiple transfusions.

Objectives: To determine the prevalence rates of alloantibodies in patients with MDS who are transfusion dependent and compare them to those of non-MDS patients matched for number of RBC units they received. 

Methods: The blood bank database was screened to identify non-MDS patients matched for age and number of units transfused. Logistic regression analysis was applied to determine factors affecting alloantibody formation. 

Results: Of 60 patients with MDS, 18 (30%) developed alloantibodies against RBC. Transfusion-dependent MDS and non-MDS patients (N=56 each), matched for number of RBC units and age, were compared. Fifteen MDS patients (27%) but only 12 non-MDS patients (12%) developed alloantibodies (P = 0.057). The relative risk for developing antibodies in MDS patients was 2.14, and MDS was the strongest predictor for formation of alloantibodies during transfusion therapy (odds ratio 3.66, confidence interval 1.4–9.3). 

Conclusions: Patients with MDS are at increased risk to develop RBC alloantibodies, partly because these patients receive multiple RBC transfusions. Whether matching for RH and KEL would lead to lower rates of RBC alloantibodies remains to be determined.