Understanding Physicians' Perceptions of Overuse of Health Services in Oncology.

Overuse rates in oncology are high, but areas of possible improvement exist for reducing it and improving quality of care. This study explores perceptions and experiences of oncologists in Israel regarding overuse of health services within oncology. In-depth, semistructured interviews were conducted focusing on causes of overuse, facilitators for reduction, and suggestions for improvement. Interviews were audio recorded, transcribed, coded, and thematically analyzed. Physicians reported patient-level causes including "well-informed" and "demanding" patients; physician-level causes including desire to satisfy patients, lack of confidence, time, and skills; and system-level causes like ease of access, and lack of alignment and coordination. Physicians can reduce overuse through patient dialogue, building trust and solidifying patient-physician relationships, and further reduce overuse with better teamwork. Improvements can be made through educational initiatives, and bottom-up solutions. Policy makers and decision makers should develop appropriate interventions addressing health service overuse, including improving patient education and instilling confidence and knowledge in physicians.

The association between adherence with oral bisphosphonates and the risk of breast cancer in post-menopausal women.

BACKGROUND: Several observational studies have suggested a protective effect of oral bisphosphonates (BP) on the risk of breast cancer, but no such association has been seen in randomized control trials. The role of oral BP in breast cancer prevention remains unclear. AIM: To investigate the association between different levels of BP exposure and breast cancer incidence in a cohort of osteoporotic post-menopausal women. SUBJECTS AND METHODS: This historical prospective study was conducted using the computerized databases of Maccabi Healthcare Services (MHS) in Israel. Included in the study were osteopenic and osteoporotic women aged 55-75 years who started BP therapy between 1998 and 2012. The subjects were enrolled in MHS for at least 3 years before therapy initiation, and had a minimum follow-up of 5 years in MHS. Women with a previous cancer, and women treated with selective estrogen receptor modulators (SERMs) were excluded. BP exposure was expressed in quintiles of proportion of days covered (PDC) with BP during follow-up period and cancer incidence was ascertained by the Israel National Tumor Registry. Person-years of follow-up began on January 1st, 1998 and ended at the date of cancer diagnosis, death, or December 31st, 2012, whichever occurred first. RESULTS: A total of 11,717 patients (mean age = 66.87 ±â€¯4.38) were eligible for the analysis. During a total of 130,252 person-years of follow-up, (mean 7.2 years) 173 incident cases of breast cancer were diagnosed. Compared to women with a PDC with BP of 20% or lower, the adjusted hazard ratio for breast cancer were HR = 0.81 (95%CI: 0.48-1.39), HR = 0.82 (95%CI: 0.50-1.33), HR = 0.72 (95%CI:0.45-1.15) and HR = 1.14 (95%CI:0.76-1.70) among women with 20-40%, 40-60%, 60%-80%, and 80% or higher, PDC, respectively. CONCLUSION: In this study, we did not find a significant association between oral BP therapy for osteoporosis and the risk of breast cancer in postmenopausal women. The discrepancy between our results and the reports of such an association in observational studies might originate from an indication bias.

Exposure to alendronate is associated with a lower risk of bone metastases in osteoporotic women with early breast cancer.

BACKGROUND: Bisphosphonate (BP) treatment to prevent bone loss in breast cancer patients is already well established. However, data on the association between oral BP exposure before cancer diagnosis and disease outcomes in patients with early breast cancer are still scarce. Limited information is available on alendronate, the most common oral agent for the treatment of post-menopausal osteoporosis, regarding the association with bone metastases. AIM: To examine the association between oral bisphosphonate exposure before cancer diagnosis and the risk of bone metastases in osteoporotic women diagnosed with early breast cancer. SUBJECTS AND METHODS: This historical cohort study was conducted at the oncology division at Tel Aviv Medical Center. The study population included post-menopausal women with early breast cancer, diagnosed between 2002 and 2012. Data on cancer characteristics, diagnosis of osteoporosis, prior bisphosphonate exposure and outcome were collected from medical files. RESULTS: Among 297 osteoporotic women identified, 145 (49%) were treated with bisphosphonates (alendronate in 90% of the cases) before cancer diagnosis. BP-treated women were significantly older than the BP-naïve ones (67.9 years vs 64.6 years, p = 0.01), but comparable in risk factors and disease characteristics. Over a mean follow up of 5.6 years, nine cases of bone metastases were identified, eight of them among BP-naïve patient (cumulative incidence of 9.9%) and one among BP-treated patients (0.7%). In a multivariable Cox's proportional hazards survival model the use of BP prior to cancer diagnosis was associated with a hazard ratio of 0.04 (95%CI:0.004-0.403, p = 0.006) for bone metastasis. The HR remained similar after further adjustment for tumor stage and cancer therapy. CONCLUSIONS: History of alendronate use is associated with a lower likelihood of bone metastases in postmenopausal women with early breast cancer. Oral bisphosphonate treatment could be sufficient for reducing the risk of bone metastases.

Cancer risk among Holocaust survivors in Israel-A nationwide study.

BACKGROUND: Holocaust survivors during World War II were exposed to various factors that are associated with cancer risk. The objective of this study was to determine whether Holocaust survivors had an increased risk for developing cancer. METHODS: The study population included 152,622 survivors. The main analysis was based on a comparison between individuals who were entitled to compensation for suffering persecution during the war and individuals who were denied such compensation. A complementary analysis compared survivors who were born in countries governed by Nazi Germany with survivors born in nonoccupied countries. A Cox proportional hazards model was used, with the time at risk of cancer development starting on either January 1, 1960, or the date of immigration to the date of cancer diagnosis or death or the date of last follow-up (December 31, 2006). RESULTS: Cancer was diagnosed in 22.2% of those who were granted compensation versus 16% of those who were denied compensation (P < .0001). Adjusting for birth cohort, sex, country of origin, and period of immigration, both analyses revealed significant increased risks of developing cancer in those who were exposed. For those who were granted versus denied compensation, the hazard ratios were 1.06 (P < .001) for all sites, 1.12 (P = .07) for colorectal cancer, and 1.37 (P = .008) for lung cancer. For those born in occupied countries versus nonoccupied countries, the hazard ratios were 1.08 (P < .001), 1.08 (P = .003), and 1.12 (P = .02), respectively. CONCLUSIONS: The current results, based on a large cohort of Holocaust survivors who were exposed to a variety of severe deprivations, add to the conflicting and sparse knowledge on this issue and support the notion that this group has a small but consistent increase in cancer development. Cancer 2017;123:3335-45. © 2017 American Cancer Society.

Dexrazoxane added to doxorubicin-based adjuvant chemotherapy of breast cancer: a retrospective cohort study with a comparative analysis of toxicity and survival.

Dexrazoxane is indicated as a cardioprotective agent for patients receiving doxorubicin who are at increased risk for cardiotoxicity. Concerns have been raised on the use of dexrazoxane, particularly in adjuvant therapy, because of the risk of interference with the antitumor effect of doxorubicin. Two meta-analyses in metastatic breast cancer have rejected this hypothesis, but have shown an apparent increase in the severity of myelosuppression when dexrazoxane is used. Here, we analyzed retrospectively a cohort of our institute database to assess whether the addition of dexrazoxane causes more bone marrow suppression in breast cancer patients receiving doxorubicin-based adjuvant therapy. The secondary objectives were assessment of the incidence of febrile neutropenia, dose-schedule modifications, recorded cardiac events or cardiac test abnormalities, and overall survival. Eight hundred and twenty-two female patients who received adjuvant (or neoadjuvant) doxorubicin and cyclophosphamide for breast cancer between 2001 and 2013 were included. One hundred and four of these patients also received dexrazoxane concurrently with the adjuvant treatment. Hospital records and, when accessible, community clinic records were reviewed. The median follow-up duration was 7 years for patients receiving dexrazoxane and 7.5 years for patients not receiving dexrazoxane. 85.6% of patients were alive at data lock. Compared with the nondexrazoxane group, patients who received dexrazoxane were older (median age at diagnosis 59 vs. 52 years) and more likely to receive dose-dense AC therapy (73 vs. 59%) and adjuvant trastuzumab treatment (29 vs. 15%). Compared with the nondexrazoxane group, dexrazoxane treatment was associated with a higher rate of hematological side effects: leukopenia (48 vs. 39%), neutropenia (45 vs. 31%, P=0.003), anemia (86 vs. 73%, P=0.005), and thrombocytopenia (37 vs. 22%, P=0.001). There were more febrile neutropenia hospitalizations (20 vs. 10%, P=0.001) and dose reductions (22 vs. 8%, P<0.001) in the dexrazoxane group, but no significant difference in the incidence of treatment delays or cancellations. The incidence of cardiac events was the same in both treatment groups with and without dexrazoxane. There was a nonsignificantly lower mortality rate in the dexrazoxane group (9.6%) compared with the nondexrazoxane group (15.0%) at data lock. Adding dexrazoxane to doxorubicin in adjuvant therapy patients leads to higher rates of bone marrow suppression in all blood components, as well as more febrile neutropenia events, and dose reductions. No differences in events defined as cardiac toxicities were detected. Dexrazoxane had no detrimental effect on survival, despite the higher hematological toxicity, the older median age, and the higher prevalence of HER2-positive disease in the dexrazoxane group.

Neo-adjuvant doxorubicin and cyclophosphamide followed by paclitaxel in triple-negative breast cancer among BRCA1 mutation carriers and non-carriers.

The purpose of this study was to assess pathological complete response and whether it serves a surrogate for survival among patients receiving neo-adjuvant doxorubicin-cyclophosphamide followed by paclitaxel for triple-negative breast cancer with respect to BRCA1 mutation status. From a neo-adjuvant systemic therapy database of 588 breast cancer cases, 80 triple-negative cases who had undergone BRCA genotyping were identified. Logistic regression model was fitted to examine the association between BRCA1 status and pathological complete response. Survival outcomes were evaluated using Kaplan-Meier method, differences between study groups calculated by log-rank test. Thirty-four BRCA1 carriers and 43 non-carriers were identified. The BRCA1 carriers had pathological complete response rate of 68 % compared with 37 % among non-carriers, p = 0.01. Yet this did not translate into superior survival for BRCA1 carriers compared with non-carriers. No difference in relapse-free survival were noted among those with or without pathological complete response in BRCA1 carriers regardless of pathological complete response status (Log-rank p = 0.25), whereas in the non-carrier cohort, relapse-free survival was superior for those achieving pathological complete response (Log-rank p < 0.0001). Response to neo-adjuvant systemic therapy differed in BRCA1-associated triple-negative breast cancer compared with triple-negative non-carriers, with a higher rate of pathological complete response. However, compared with non-carrier triple-negative breast cancer, pathological complete response was not a surrogate for superior relapse-free survival in BRCA1 patients. Future studies using specific chemotherapy regimens may provide further improvements in outcomes.

Population-based screening for breast and ovarian cancer risk due to BRCA1 and BRCA2.

In the Ashkenazi Jewish (AJ) population of Israel, 11% of breast cancer and 40% of ovarian cancer are due to three inherited founder mutations in the cancer predisposition genes BRCA1 and BRCA2. For carriers of these mutations, risk-reducing salpingo-oophorectomy significantly reduces morbidity and mortality. Population screening for these mutations among AJ women may be justifiable if accurate estimates of cancer risk for mutation carriers can be obtained. We therefore undertook to determine risks of breast and ovarian cancer for BRCA1 and BRCA2 mutation carriers ascertained irrespective of personal or family history of cancer. Families harboring mutations in BRCA1 or BRCA2 were ascertained by identifying mutation carriers among healthy AJ males recruited from health screening centers and outpatient clinics. Female relatives of the carriers were then enrolled and genotyped. Among the female relatives with BRCA1 or BRCA2 mutations, cumulative risk of developing either breast or ovarian cancer by age 60 and 80, respectively, were 0.60 (± 0.07) and 0.83 (± 0.07) for BRCA1 carriers and 0.33 (± 0.09) and 0.76 (± 0.13) for BRCA2 carriers. Risks were higher in recent vs. earlier birth cohorts (P = 0.006). High cancer risks in BRCA1 or BRCA2 mutation carriers identified through healthy males provide an evidence base for initiating a general screening program in the AJ population. General screening would identify many carriers who are not evaluated by genetic testing based on family history criteria. Such a program could serve as a model to investigate implementation and outcomes of population screening for genetic predisposition to cancer in other populations.

Parametric diffusion tensor imaging of the breast.

OBJECTIVES: To investigate the ability of parametric diffusion tensor imaging (DTI), applied at 3 Tesla, to dissect breast tissue architecture and evaluate breast lesions. MATERIALS AND METHODS: All protocols were approved and a signed informed consent was obtained from all subjects. The study included 21 healthy women, 26 women with 33 malignant lesions, and 14 women with 20 benign lesions. Images were recorded at 3 Tesla with a protocol optimized for breast DTI at a spatial resolution of 1.9 × 1.9 × (2-2.5) mm3. Image processing algorithms and software, applied at pixel resolution, yielded vector maps of prime diffusion direction and parametric maps of the 3 orthogonal diffusion coefficients and of the fractional anisotropy and maximal anisotropy. RESULTS: The DTI-derived vector maps and parametric maps revealed the architecture of the entire mammary fibroglandular tissue and allowed a reliable detection of malignant lesions. Cancer lesions exhibited significantly lower values of the orthogonal diffusion coefficients, λ1, λ2, λ3, and of the maximal anisotropy index λ1-λ3 as compared with normal breast tissue (P < 0.0001) and to benign breast lesions (P < 0.0009 and 0.004, respectively). Maps of λ1 exhibited the highest contrast-to-noise ratio enabling delineation of the cancer lesions. These maps also provided high sensitivity/specificity of 95.6%/97.7% for differentiating cancers from benign lesions, which were similar to the sensitivity/specificity of dynamic contrast-enhanced magnetic resonance imaging of 94.8%/92.9%. Maps of λ1-λ3 provided a secondary independent diagnostic parameter with high sensitivity of 92.3%, but low specificity of 69.5% for differentiating cancers from benign lesions. CONCLUSION: Mapping the diffusion tensor parameters at high spatial resolution provides a potential novel means for dissecting breast architecture. Parametric maps of λ1 and λ1-λ3 facilitate the detection and diagnosis of breast cancer.

Association between very young age and adverse characteristics of breast cancer at presentation amongst Israeli women.

BACKGROUND: Up to 4% of breast cancer cases occur in women younger than 35 years. Studies have suggested an association between breast cancer at a young age, poorer outcome, and adverse clinical and pathologic characteristics. It is unclear whether age is an independent prognostic factor. OBJECTIVES: To characterize the prognostic significance of young age at diagnosis through comparison of disease characteristics of "less-young" (born between 1958-1962 and aged 37-44 years) and "very-young" (born after 1967 and aged ≤35 years) premenopausal patients. METHODS: Consecutive patients with breast cancer born after 1967 treated at Sheba Medical Centre between January, 1999 and October, 2002 were identified and their files reviewed. This cohort was identified as "very-young" and was compared with a group of "less-young" patients. The clinico-pathologic characteristics and survival data were compared. RESULTS: Sixty-one very young and 94 less-young patients were identified. The mean age at diagnosis was 29.9 (range, 23-34 years) and 40.5 years (range, 37-44 years) for the very young and less young patients, respectively (P < 0.0001). Significantly more very young patients had metastatic disease at presentation (20% vs. 3%, respectively, P = 0.0007). The very young patients were more likely to have high grade, endocrine nonresponsive tumors than the less young patients. After controlling for stage and tumor grade, very-young age was not shown to be an independent risk factor for reduced survival. CONCLUSIONS: Very young age among Israeli women with breast cancer is associated with higher stage at diagnosis, adverse pathologic characteristics and adverse outcome but is not an independent prognostic factor for survival.

Immunosuppressive treatments reduce long-term immunity to smallpox among patients with breast cancer.

BACKGROUND: Mass vaccination is the principal preventive measure against a smallpox outbreak after an act of bioterrorism. Vaccination of subjects who received immunosuppressive therapies is problematic because of smallpox vaccine reactogenicity. Moreover, long-term immunity to vaccinia might be affected. OBJECTIVE: The objective of the study was to examine the effect of cytotoxic chemotherapy on long-term immunity to vaccinia. METHODS: In a case-control study, 67 patients with breast cancer who received cytotoxic chemotherapy and who were disease free for at least 1 year were matched with healthy controls according to age, sex, and the number of smallpox vaccinations received. Markers of immunity to smallpox were examined. Forty-one patients with breast cancer who did not receive chemotherapy were used to assess the affect of cancer and radiotherapy on immunity to smallpox. RESULTS: Patients with breast cancer who received chemotherapy had lower levels of vaccinia total immunoglobulin G and immunoglobulin G1 (expressed as enzyme-linked immunosorbent assay units per milliliter), neutralizing antibodies, vaccinia:memory B cell ratio (expressed as a percentage), and interferon-gamma level (expressed as picograms per milliliter), compared with healthy control individuals. CONCLUSIONS: Immunity to smallpox is reduced after receipt of chemotherapy for breast cancer. This finding should be considered when planning smallpox vaccination campaigns. The effect of immunosuppressive treatments on persistence of immunity should be tested with respect to additional vaccines or natural infections.

Clinical responses in a phase II study using adoptive transfer of short-term cultured tumor infiltration lymphocytes in metastatic melanoma patients.

PURPOSE: Adoptive cell therapy with autologous tumor-infiltrating lymphocytes (TIL) has shown promising results in metastatic melanoma patients. Although objective response rates of over 50% have been reported, disadvantages of this approach are the labor-intensive TIL production and a very high drop-out rate of enrolled patients, limiting its widespread applicability. Previous studies showed a clear correlation between short TIL culture periods and clinical response. Therefore, we used a new TIL production technique using unselected, minimally cultured, bulk TIL (Young-TIL). The use of Young-TIL is not restricted to human leukocyte antigen (HLA)-A2 patients. The purpose of this study is to explore the efficacy and toxicity of adoptively transferred Young-TIL following lympho-depleting chemotherapy in metastatic melanoma patients, refractory to interleukin-2 and chemotherapy. EXPERIMENTAL DESIGN: Young-TIL cultures for 90% of the patients were successfully generated, enabling the treatment of most enrolled patients. We report here the results of 20 evaluated patients. RESULTS: Fifty percent of the patients achieved an objective clinical response according to the Response Evaluation Criteria in Solid Tumors, including two ongoing complete remissions (20+, 4+ months) and eight partial responses (progression-free survival: 18+, 13+, 10+, 9, 6+, 4, 3+, and 3 months). All responders are currently alive. Four additional patients showed disease stabilization. Side effects were transient and manageable. CONCLUSION: We showed that lympho-depleting chemotherapy followed by transfer of short-term cultured TIL can mediate tumor regression in 50% of metastatic melanoma with manageable toxicity. The convincing clinical results combined with the simplification of the process may thus have a major effect on cell therapy of cancer.

The management of cancer pain in the elderly.

Cancer pain in the elderly population is an increasingly common clinical situation which physicians are challenged with managing. Physiological changes occur with ageing affecting the patients' perception of pain, their ability to describe pain and also their metabolism of drugs. As a general rule, the elderly should be treated according to their physiological age rather than their chronological age. This also applies to decisions regarding anti-tumor treatments such as chemotherapy. Analgesics should also be used with care in the elderly as the elderly are generally more susceptible to larger changes in doses and to drug side effects. However, this should not deter the use of analgesics, in particular opioids, in the treatment of elderly patients who suffer from cancer related pain.

Hormone receptor expression is associated with a unique pattern of metastatic spread and increased survival among HER2-overexpressing breast cancer patients.

OBJECTIVES: HER2/neu (HER2) overexpression occurs in approximately 20% of breast cancers and is associated with aggressive disease. Although a significant number of HER2-positive tumors also express hormone receptors (HR), the effects HR expression has on clinical characteristics, including response to trastuzumab among HER2-positive breast cancer, has not been elucidated yet. METHODS: A retrospective analysis of consecutive metastatic HER2-positive breast cancer patients was conducted in 2 medical centers. Associations between hormone receptors expression and clinical variables, and metastatic spread pattern and survival were studied. RESULTS: The study population included 137 metastatic HER2-positive breast cancer patients, 56 of them were HR-positive and 81 were HR-negative. No significant differences between the 2 groups were found for demographic and clinical characteristics, including age, stage at diagnosis, tumor histology, and grade. Similar response rate to trastuzumab was observed in both study groups. Significantly, longer, median, disease-free, and overall survival was noted among the HR-positive patients. Patients in the HR-negative group had significantly more liver metastases, a trend for more brain metastases, and less bone metastases. There was a strong trend for more visceral metastases in the HR-negative group. CONCLUSIONS: Our results suggest an important role for HR expression in modulating metastases predilection and disease progression in HER2-positive breast cancer.

Germline analysis of thymidine/guanidine polymorphism at position 309 of the Mdm2 promoter in malignant melanoma patients.

p53 is a major tumor suppressor gene, frequently mutated in human cancer, but rarely mutated in malignant melanoma (MM). Mdm2, the major negative regulator of p53, is overexpressed in 50-60% of MM patients, by an unknown mechanism. Single nucleotide polymorphism at position 309 of the Mdm2 promoter correlates with increased Mdm2 levels and reduced p53 activation. We speculated that guanine at position 309 (G309) of the Mdm2 promoter might be a cause of Mdm2 overexpression in MM patients, and associated with increased risk of MM. We aimed to estimate the prevalence of G309 in MM patients. Genomic DNA was collected from a cohort of 28 MM patients of various clinical stages. The relevant DNA stretch was sequenced and thymidine/guanidine polymorphism at position 309 of Mdm2 promoter was examined. We compared the resultant frequencies with the frequencies reported in the literature for the general population. The G allele frequency in the cohort of MM patients was 0.518. This frequency is high compared with the reported frequency of 0.351 in Caucasian healthy populations (odds ratio=1.98, P=0.014). It is also higher than a G allele frequency of 0.464 reported for Ashkenazi Jewish women, although this comparison was not statistically significant (odds ratio=1.14, P=0.76). These results suggest that the single nucleotide polymorphism G309 in the Mdm2 promoter might be an important genetic predisposing factor, and possibly indicate a molecular mechanism of disease regarding MM. These results must be confirmed in a larger cohort of MM patients and controls.

Minimally cultured or selected autologous tumor-infiltrating lymphocytes after a lympho-depleting chemotherapy regimen in metastatic melanoma patients.

Adoptive cell therapy with autologous tumor-infiltrating lymphocytes (TIL) and high-dose interleukin-2 (IL-2), after nonmyeloablative chemotherapy, has been shown to result in tumor regression in half of refractory metastatic melanoma patients. In the present study, we describe 2 separate clinical protocols. Twelve patients were treated with "Selected"-TIL, as previously reported and 8 patients with the modified version of "Young"-TIL. Selected-TIL protocol required the establishment of multiple T-cell cultures from 1 patient and in vitro selection of cultures secreting interferon-gamma upon antigenic stimulation. In contrast, Young-TIL are minimally cultured T cells with superior in vitro features that do not require further selection. Two of 12 Selected-TIL patients experienced objective clinical responses (1 complete response, 1 partial response). Out of 8 treated Young-TIL patients, 1 experienced complete response, 2 partial response, and 4 patients had disease stabilization. Twenty-one of 33 enrolled Selected-TIL patients were excluded from the protocol, mainly as cultures failed the interferon-gamma selection criteria or due to clinical deterioration, compared with only 3 Young-TIL patients. Expected bone marrow suppression and high-dose IL-2 toxicity were transient. There was no treatment-related mortality. This study vindicates the feasibility and effectiveness of TIL technology and calls for further efforts to implement and enhance this modality. The use of minimally cultured, unselected Young-TIL enables the treatment of most enrolled patients. Although the cohort of Young-TIL patients treated so far is rather small and the follow-up short, the response rate is encouraging.

Pain palliation in patients with bone metastases using MR-guided focused ultrasound surgery: a multicenter study.

BACKGROUND: Noninvasive thermal ablation using magnetic resonance (MR)-guided focused ultrasound (MRgFUS) has been shown to be clinically effective in uterine fibroids, and is being evaluated for ablation of breast, liver, and brain lesions. Recently MRgFUS has been evaluated for palliation of pain caused by bone metastases. We present the clinical results of a multicenter study using MRgFUS for palliation of bone metastases pain. METHODS: A multicenter study to evaluate the safety and efficacy of MRgFUS palliative treatment of bone metastases was conducted in patients suffering from painful metastatic bone lesions for which other treatments were either ineffective or not feasible. Thirty-one patients with painful bone metastases underwent the MRgFUS procedure in three medical centers. Treatment safety was evaluated by assessing the device-related complications. Effectiveness of pain palliation was evaluated using the visual analog pain score (VAS), and measurable changes in the intake of opioid analgesics. RESULTS: Thirty-six procedures were performed on 31 patients. Mean follow-up time was 4 months. 25 patients underwent the planned treatment and were available for 3 months post-treatment follow-up. 72% of the patients (18/25) reported significant pain improvement. Average VAS score was reduced from 5.9 prior to treatment to 1.8 at 3 months post treatment. 67% of patients with recorded medication data reported a reduction in their opioid usage. No device-related severe adverse events were recorded. CONCLUSION: The results suggest that MRgFUS has the ability to provide an accurate, effective, and safe noninvasive palliative treatment for patients with bone metastases.

Concurrent chemobiotherapy with cisplatin, dacarbazine, decrescendo interleukin-2 and interferon alpha2b in patients with metastatic melanoma.

We aimed to evaluate a concurrent chemobiotherapy (CBT) regimen consisting of cisplatin (CDDP), dacarbazine (DTIC), decrescendo interleukin-2 (IL-2), and interferon alpha2b (INF-alpha2b), in metastatic melanoma patients. A total of 60 patients with biopsy proven, metastatic melanoma were treated between October 2000 and November 2005 at the Oncology Institutes of RMC and CSMC. Patients received concurrent CBT for 5 days, consisting of CDDP, DTIC, decrescendo IL-2, and subcutaneous INF-alpha2b. GM-CSF was given subcutaneously on days 8 to 12 of each cycle, to the first 26 patients. Treatment was administered q21d for a total of six cycles or until severe toxicity or progression; 57 patients who received at least two cycles, followed for at least 24 months, were included in response analysis. The overall response rate (RR) reached 44% (28/57 patients); 14 patients had a complete response (CR, 25%); 11 (19%) reached a partial response. The median progression-free survival was 7 months. Median overall survival (OS) was 11.7 months. At a median follow-up of 29 months, 8 of 14 complete responders remain alive for more than two years, with no clinical evidence of disease. Median OS of patients with CR has not been reached; 17% of the courses were modified due to toxicity, and 20% of the patients were removed from the protocol due to toxicity or refusal to continue. The data from this study indicate that this protocol of concomitant CBT is feasible with a fraction of the patients achieving a durable CR.

Adjuvant chemotherapy and whole abdominal irradiation for gastric carcinoma.

AIMS AND BACKGROUND: To analyze the efficacy and toxicity of adjuvant chemotherapy followed by whole abdominal irradiation in the treatment of resectable gastric cancer with positive lymph nodes. METHODS AND STUDY DESIGN: Between 1996 and 1999, 10 patients with node-positive gastric cancer underwent complete gross resection and were treated by postoperative chemoradiotherapy. The chemotherapy regimen consisted of 5-fluorouracil, 1000 mg/m2/day as a 96-hr continuous infusion on day 1, and cisplatin, 100 mg/m2 on day 2, every 21 days. Six courses were planned. Radiotherapy was administered 3 weeks after completion of the chemotherapy protocol as a single-fraction dose of 600 cGy in a two-field (anterior and posterior) configuration. RESULTS: Treatment was generally well tolerated, with no treatment-related deaths. However, 9 of the 10 patients died of recurrent disease, with a median survival of 20 months (range, 7-84). CONCLUSIONS: Adjuvant chemotherapy with whole abdominal irradiation for gastric cancer is safe and tolerable but has no apparent effect on patient outcome. Studies in larger series are needed to evaluate the role of the approach in this disease.

[Three-dimensional conformal radiation therapy concurrent with full dose Gemcitabine for locally advanced inoperable pancreatic cancer].

BACKGROUND: Gemcitabine is a potent radiosensitizer of pancreatic cancer cells. Concomitant full dose Gemcitabine and three dimensional conformal radiation to a small field is a novel approach to unresectable locally advanced pancreatic cancer. The aim of this study is to report the outcome, tolerability and toxicity of this combined therapy. METHODS: A retrospective chart review, with survival data confirmed by the population registry and statistic analysis was performed with SPSS. Radiotherapy was planned using computerized tomography, treated only the gross tumor without regional lymph nodes and was delivered in 15 fractions of 2.4 Gy to a dose of 36 Gy. Gemcitabine was administered weekly during radiation at a dose of 1000 mg/m2. Gastrointestinal toxicity was scored according to the NCI Common Toxicity Criteria. Local control was assessed by RECIST criteria, a partial response defined as a decrease of at least 30% in the longest diameter of the tumor. RESULTS: Eighteen of the 19 patients completed treatment as planned without the need for treatment break. Four patients subsequently developed severe grade III-IV gastrointestinal toxicity; 37% of patients achieved a partial response and 52% experienced significant clinical benefit. The median survival was 11.7 months. DISCUSSION: Full dose gemcitabine with conformal 3-D radiotherapy to a small field was well tolerated and was associated with a low incidence of severe gastrointestinal toxicity compared with previous studies of combination therapy using standard large radiation portals which encompass both the tumor and the regional lymph nodes. A partial response was observed in over one third of patients, non-progression of the irradiated tumor in the rest with pain relief and clinical benefit in more than half the patients. CONCLUSION: This treatment approach was well tolerated with little morbidity and achieves outcomes equal to or better than other contemporary combination modality approaches.