Israel Medical Association Journal

Objectives: To evaluate the feasibility of induction chemotherapy with docetaxel-cisplatin-5-flurouracil (TPF) followed by external beam radiotherapy (EBRT) with concomitant chemotherapy (CRT) or cetuximab (ERT) in the treatment of patients with advanced SCCHN.

Methods: We reviewed the data of all patients with advanced SCCHN, stage III and IV, treated in 2007–2010. Tolerability was assessed and scored according to the proportion of patients completing the planned study protocol. Toxicity was scored using the U.S. National Cancer Institute Common Toxicity Criteria (version 4) for classification of adverse events.

Results: The study included 53 patients. TPF was initiated at a reduced dose in 13 patients (25%). Twenty-two patients (41.5%) received primary prophylaxis with granulocyte colony-stimulating factor (GCSF) and 42 (77%) completed treatment according to schedule. During the induction phase one patient (2%) died and 24 (45%) had one or more grade 3-4 complications. The number of patients who developed neutropenia was lower in the group that received primary GCSF prophylaxis. Secondary dose reductions were required in 21% of the patients.

Conclusions: Induction TPF was associated with grade 3-4 toxicity. Prophylaxis with GCSF should be part of the treatment regimen.

Objectives: To report our first year experience with a CPU located in an internal medicine department as compared to the year before establishment of the CPU.

Methods: We retrospectively evaluated the medical records of consecutive patients who were admitted to our internal medicine department for the investigation of chest pain for 2 different years: a year before and a year after the establishment of the CPU in the department. We focused on the patients' characteristics and the impact of the CPU regarding the investigational modalities used and the length of in-hospital stay.

Results: In the year before establishment of the CPU, 258 patients were admitted to our department with chest pain, compared to 417 patients admitted to the CPU in the first year of its operation. All patients were followed for serial electrocardiographic and cardiac enzyme testing. All CPU patients (100%) underwent investigation compared to only 171 patients (66%) in the pre-CPU year. During the year pre-CPU, 164 non-invasive tests were performed (0.64 tests per patient) compared to 506 tests (1.2 tests/patient) in the CPU population. Coronary arteriography was performed in 35 patients (14%) during the pre-CPU year, mostly as the first test performed, compared to 61 patients (15%) during the CPU year, mostly as a second test, with only 5 procedures (1.1%) being the first test performed. The length of hospitalization was significantly shorter during the CPU year, 37.8 ± 29.4 hours compared to 66.8 ± 46 hours in the pre-CPU year.

Conclusions: Establishment of a CPU in an internal medicine department significantly decreased the need for invasive coronary arteriography as the first modality for investigating patients admitted with chest pain, significantly decreased the need for invasive procedures (especially where no intervention was performed), and significantly shortened the hospitalization period. CPU is an effective facility for rapid and effective investigation of patients admitted with chest pain. 

Objectives: To retrospectively determine the clinical response to ¹³¹I-MIBG therapy at low doses in patients with refractory neuroblastoma.

Methods: We performed a retrospective chart review of 10 patients with neuroblastoma treated with ¹³¹I-MIBG at Rambam Health Care Campus from 1994 to 2012. Clinical data, number of ¹³¹I-MIBG courses delivered, toxicities, and clinical responses were reviewed. MIBG scan was performed after each course.

Results: Twenty-one courses of ¹³¹I-MIBG were delivered to 10 patients (3 girls, 7 boys). Their mean age was 3.8 years (range 1.5–6 years). All patients received several protocols of chemotherapy including the high dose form. Three patients received three courses of ¹³¹I-MIBG with a minimum of 6 weeks between each course, five patients received two courses, and two patients received only one course. An objective response to the first course was obtained in nine patients and to the second course in six of eight, and in three children who underwent the third course the pain decreased. One patient has no evidence of disease, four are alive with disease, and five died of the disease. No unanticipated toxicities were observed.

Conclusions: Low dose ¹³¹I-MIBG is an effective and relatively non-toxic treatment in neuroblastoma disease palliation. Rapid and reproducible pain relief with ¹³¹I-MIBG was obtained in most of the children. Treatment with systemic radiotherapy in the form of low dose ¹³¹I-MIBG was easy to perform and effective in cases of disseminated neuroblastoma, demonstrating that this primary therapy can be used for palliative purposes.

 Background: Vitamin D status is not evaluated routinely in cancer patients with bone metastasis who are treated with bisphosphonates.

Objectives: To assess the effect of vitamin D status on risk of hypocalcemia and quality of life in these patients.

Methods: We performed laboratory tests for routine serum biochemistry, 25(OH)D, plasma parathyroid hormone (PTH) and bone turnover markers (CTX, P1NP) in 54 patients aged 57.5 ± 13 years treated with intravenous bisphosphonates.

Results: Most of the patients (n=44, 77.8%) did not receive calcium and vitamin D supplementation. Their mean serum 25(OH)D levels (12.83 ± 6.86 ng/ml) correlated with vitamin D daily intake (P = 0.002). In 53 patients (98.1%) 25(OH)D levels were suboptimal (< 30 ng/ml). Albumin-corrected calcium levels correlated with plasma PTH (P = 0.001). No correlation was observed between daily calcium intake and serum calcium (P = 0.45). Hypocalcemia was observed in one patient. Mean plasma PTH was 88.5 ± 65 ng/L. Plasma PTH correlated negatively with 25(OH)D serum levels (P = 0.003) and positively with P1NP (P = 0.004). Albumin-corrected calcium correlated negatively with P1NP (mean 126.9 ± 191 ng/ml) but not with CTX levels (mean 0.265 ± 0.1 ng/ml) (P < 0.001). There was no correlation among quality of life parameters, yearly sun exposure and 25(OH)D levels (P = 0.99).

Conclusions: Vitamin D deficiency is frequent in oncology patients with bone metastasis treated with bisphosphonates and might increase bone damage. Our results indicate a minor risk for the development of severe hypocalcemia in vitamin D-deficient patients receiving bisphosphonate therapy. Although vitamin D deficiency might have some effect on the quality of life in these patients, it was not proven significant.
 

Background: Defibrillation threshold (DFT) testing at the time of implantable cardioverter defibrillator (ICD) insertion is performed routinely. Recently this practice is being reconsidered due to doubts about its ability to improve ICD efficacy and evidence that survival may not be affected by the test.

Objectives: To compare the outcome of ICD recipients who underwent DFT testing and those in whom no testing was performed.

Methods: A total of 213 eligible patients were implanted with an ICD between 2004 and 2009. DFT testing was performed in 80. We compared total mortality, appropriate and inappropriate ICD shocks, and anti-tachycardia pacing (ATP) events between DFT and non-DFT patients during a follow-up of 2 years.

Results: On comparing the DFT and non-DFT groups, we found a 2 year mortality rate of 7.5% versus 8.3%, respectively (P = 0.8). Furthermore, 20.7% of patients in the DFT group and 12.4% in the non-DFT group had at least one episode of ICD shock (P = 0.15). With regard to ICD treatment (ICD shocks or ATP events), 57.7% in the DFT group and 64.2% in the non-DFT group received appropriate treatments (P = 0.78).

Conclusions: No significant differences in the incidence of 2 year mortality or percentage of ICD treatment emerged between the DFT and non-DFT groups.
 

Background: Adjuvant/neoadjuvant chemotherapy in breast cancer patients may be associated with amenorrhea and a marked reduction in ovarian reserve.

Objectives: To assess the use of letrozole with follicle-stimulating hormone (FSH) in gonadotropin-releasing hormone (GnRH) analogue protocols, based on reported attempts to avoid the estradiol (E2) increase during controlled ovarian hyperstimulation for embryo cryopreservation in breast cancer patients using a combination of low dose FSH and aromatase inhibitor (letrozole) in a GnRH-antagonist protocol.

Methods: Twenty-four breast cancer patients were treated with recombinant FSH (150–450 U/day) and letrozole (5 mg/day) in a long GnRH-agonist (n=7) or GnRH-antagonist (n=17) protocol. After oocyte retrieval, insemination and/or intracytoplasmic sperm injection was performed. The embryos were frozen.

Results: The average interval from surgery to oocyte retrieval was 40 days. Average duration of treatment was 9.6 days and mean peak E2 level 1342 ± 1091 pmol/L, yielding 16.0 ± 16.3 oocytes (range 0–82). Mean fertilization rate was 69.5 ± 20.4% and mean number of embryos cryopreserved 10.3 ± 9.3. More oocytes were retrieved with the long GnRH protocol, but the difference was not statistically significant (24.8 ± 24.6 vs. 12.0 ± 8.8 pmol/L, P = 0.07).

Conclusions: As previously reported, ovarian stimulation with letrozole and FSH, in both the long GnRH-agonist and GnRH-antagonist protocols, is apparently effective in breast cancer patients and spares them exposure to high E2 levels.
 

Background: Epidemiological studies have found that intrauterine growth retardation (IUGR) is closely related to hypertension and is associated with a reduced number of nephrons that may be a predisposing factor for the development of hypertension.

Objectives: To determine whether blood pressure levels of children with a history of IUGR are higher than those of children without IUGR.

Methods: Diastolic, systolic and mean arterial blood pressure levels were measured in 64 children aged 8–12 years old with a history of IUGR (mean birth weight 1780 ± 422 g) and compared with 64 age and gender-matched controls who had a normal birth weight (mean 3134 ±  594 g).

Results: Contrary to previous reports, systolic blood pressure values were significantly lower in the IUGR group compared to the controls (91.6 ±11.3 vs. 96.6 ±13.9, P = 0.027). There was no difference in diastolic blood pressure values. In the IUGR group, systolic blood pressure correlated significantly with current weight (P < 0.01) and body mass index (P < 0.05), and diastolic blood pressure with weight gain between age 2 and 4 years (P < 0.05). None of the blood pressure values correlated with birth weight.

Conclusions: Children born with IUGR have lower systolic blood pressure levels than matched controls at age 8–12 years. These data indicate that postnatal weight gain in this group has a greater impact on systolic blood pressure than birth weight.
 

Background: Survival in T cell lymphoblastic lymphoma has improved over the past 30 years, largely due to treatment protocols derived from regimens designed for children with acute lymphoblastic leukemia.

Objectives: To assess the outcome of the NHL-BFM-95 protocol in children and adolescents hospitalized during the period 1999–2006.

Methods: We conducted a retrospective multi-institutional, non-randomized study of children and adolescents up to age 21 with T cell lymphoma admitted to pediatric departments in six hospitals in Israel, with regard to prevalence, clinical characteristics, pathological characteristics, prognostic factors, overall survival (OS) and event-free survival (EFS). All patients had a minimal follow-up of one year after diagnosis. The study was based on the NHL[1]-BFM[2]-95 protocol.

Results: At a median follow-up of 4 years (range 1–9 years), OS and EFS for all patients was 86.5% and 83.8%, respectively. OS was 86.7% and 83.3% for patients with stage III and stage IV, respectively, and EFS was 83.3% and 83.3%, respectively. EFS was 62.5% for Arab patients and 89.7% for Jewish patients (P = 0.014). Patients who did not express CD45 antigen showed superior survival (P = 0.028). Five (13.5%) patients relapsed, four of whom died of their disease. Death as a consequence of therapy toxicity was documented in one patient while on the re-induction protocol (protocol IIA).

Conclusions: Our study shows that OS and EFS for all patients was 86.5% and 83.8%, respectively.