Prophylactic irradiation to the contralateral breast for BRCA mutation carriers with early-stage breast cancer.

BACKGROUND: Women who carry germ-line mutations in BRCA1/2 are at very high risk of developing breast and ovarian cancer. Breast conserving therapy is associated with a similar risk of ipsilateral cancer recurrence in BRCA carriers compared with non-carriers. However, the risk of subsequent contralateral breast cancer in carriers is markedly increased. Therefore, mastectomy of the diseased breast along with risk reducing mastectomy of the contralateral breast is often advocated for BRCA carriers who are treated for early breast cancer. Yet, many BRCA carriers forgo this option for fear of harmful effects and choose breast conserving treatment and observation instead. In Israel, BRCA-associated breast cancer is relatively common. Accordingly, a national protocol was devised for this enriched population. PATIENTS AND METHODS: In this Institutional Review Board-approved phase II trial, the option of prophylactic irradiation to the contralateral breast, in addition to standard loco-regional treatment, was offered to BRCA carrier patients treated for early breast cancer who declined contralateral mastectomy. The primary end point was contralateral breast cancer. RESULTS: Between May 2007 and October 2017, 162 patients were enrolled. Eighty-one patients opted for standard loco-regional treatment including surgery and radiation to the involved side (control arm) and 81 patients chose additional contralateral breast irradiation (intervention arm). At a median follow-up of 58 months, 10 patients developed contralateral breast cancer in the control arm at a median of 32 months, as compared with 2 patients in the intervention arm who developed contralateral breast cancer 80 and 105 months after bilateral breast irradiation (log-rank P = 0.011). CONCLUSIONS: Among BRCA carrier patients treated for early breast cancer, the addition of contralateral breast irradiation was associated with a significant reduction of subsequent contralateral breast cancers and a delay in their onset. CLINICAL TRIAL: Phase II, comparative two-arm trial (NCT00496288).

Total Skin Electron Irradiation and Sequential Malignancies in Mycosis Fungoides Patients: Longitudinal Study.

AIMS: To determine the role of total skin electron irradiation (TSEI) as a cause of second malignancies in mycosis fungoides patients. MATERIALS AND METHODS: Mycosis fungoides patients referred to TSEI were followed in a longitudinal study. Other diagnosed malignancies were obtained after cross-matching with the Israel National Cancer Registry database. RESULTS: Between 1974 and 2010, 197 patients were treated: 134 (68%) men, 63 (32%) women; mean age 58 ± 17years. Topical/systemic treatment was given to 134 (68%) patients. TSEI was given to 104 (68.9%) patients. Seven (4.6%) received sub-TSEI and 40 (26.5%) received focal electron irradiation fields. Forty-six (23%) patients did not receive radiotherapy. The second primaries rate was 6.7 times higher in male mycosis fungoides patients and 13.1 times higher in female mycosis fungoides patients than in the general Israeli population. Malignant melanoma developed in eight patients after radiotherapy, in one patient without irradiation. The skin-related cancer rate after irradiation versus no irradiation was higher (P = 0.018). Combination radiotherapy with psoralen + ultraviolet A and/or nitrogen mustard yielded 11 cases of skin cancer versus no cases without irradiation. CONCLUSIONS: Mycosis fungoides patients have a high incidence of sequential malignancies. TSEI is associated with higher 'skin-related cancer' rates. Close longitudinal follow-up of mycosis fungoides patients is obligatory.

Patterns of practice of regional nodal irradiation in breast cancer: results of the European Organization for Research and Treatment of Cancer (EORTC) NOdal Radiotherapy (NORA) survey.

BACKGROUND: Predicting outcome of breast cancer (BC) patients based on sentinel lymph node (SLN) status without axillary lymph node dissection (ALND) is an area of uncertainty. It influences the decision-making for regional nodal irradiation (RNI). The aim of the NORA (NOdal RAdiotherapy) survey was to examine the patterns of RNI. METHODS: A web-questionnaire, including several clinical scenarios, was distributed to 88 EORTC-affiliated centers. Responses were received between July 2013 and January 2014. RESULTS: A total of 84 responses were analyzed. While three-dimensional (3D) radiotherapy (RT) planning is carried out in 81 (96%) centers, nodal areas are delineated in only 51 (61%) centers. Only 14 (17%) centers routinely link internal mammary chain (IMC) and supraclavicular node (SCN) RT indications. In patients undergoing total mastectomy (TM) with ALND, SCN-RT is recommend by 5 (6%), 53 (63%) and 51 (61%) centers for patients with pN0(i+), pN(mi) and pN1, respectively. Extra-capsular extension (ECE) is the main factor influencing decision-making RNI after breast conserving surgery (BCS) and TM. After primary systemic therapy (PST), 49 (58%) centers take into account nodal fibrotic changes in ypN0 patients for RNI indications. In ypN0 patients with inner/central tumors, 23 (27%) centers indicate SCN-RT and IMC-RT. In ypN1 patients, SCN-RT is delivered by less than half of the centers in patients with ypN(i+) and ypN(mi). Twenty-one (25%) of the centers recommend ALN-RT in patients with ypN(mi) or 1-2N+ after ALND. Seventy-five (90%) centers state that age is not considered a limiting factor for RNI. CONCLUSION: The NORA survey is unique in evaluating the impact of SLNB/ALND status on adjuvant RNI decision-making and volumes after BCS/TM with or without PST. ALN-RT is often indicated in pN1 patients, particularly in the case of ECE. Besides the ongoing NSABP-B51/RTOG and ALLIANCE trials, NORA could help to design future specific RNI trials in the SLNB era without ALND in patients receiving or not PST.

Primary signet-ring cell adenocarcinoma of the uterine cervix: case report and review of the literature.

Signet-ring cell adenocarcinoma is a rare subtype of the uterine cervix; thus there are no guidelines and the prognosis is unknown. There seems to be a significant role for reporting the treatment and outcome of this rare disease in order to establish guidelines and to assist in decision-making. However, treatment should be tailored to each patient according to clinical status and disease stage. Excluding extra-genital origin is mandatory, as it will change treatment management considerably.

Clinical and technical characteristics of intraoperative radiotherapy. Analysis of the ISIORT-Europe database.

BACKGROUND: A joint analysis of clinical data from centres within the European section of the International Society of Intraoperative Radiation Therapy (ISIORT-Europe) was undertaken in order to define the range of intraoperative radiotherapy (IORT) techniques and indications encompassed by its member institutions. MATERIALS AND METHODS: In 2007, the ISIORT-Europe centres were invited to record demographic, clinical and technical data relating to their IORT procedures in a joint online database. Retrospective data entry was possible. RESULTS: The survey encompassed 21 centres and data from 3754 IORT procedures performed between 1992 and 2011. The average annual number of patients treated per institution was 42, with three centres treating more than 100 patients per year. The most frequent tumour was breast cancer with 2395 cases (63.8 %), followed by rectal cancer (598 cases, 15.9 %), sarcoma (221 cases, 5.9 %), prostate cancer (108 cases, 2.9 %) and pancreatic cancer (80 cases, 2.1 %). Clinical details and IORT technical data from these five tumour types are reported. CONCLUSION: This is the first report on a large cohort of patients treated with IORT in Europe. It gives a picture of patient selection methods and treatment modalities, with emphasis on the main tumour types that are typically treated by this technique and may benefit from it.

Radiotherapy as sole adjuvant treatment for older patients with low-risk breast cancer.

Partly as a result of screening, increasing numbers of older patients are presenting with 'low risk' breast cancer: tumours from which the likelihood of breast cancer death is minute; even so, these patients have a measurable risk of local recurrence if conservative surgery is not followed by some form of adjuvant treatment. However, it must be acknowledged that any such treatment has no detectable impact upon survival, and the value of all such interventions must be considered in the context of the individual patient's non-cancer life expectancy and the complex psychosocial factors that affect older patients. If no impact on survival can be expected and the risk of local recurrence is high enough to warrant some post-operative treatment, the most powerful agent in this respect is radiotherapy. Whilst adjuvant endocrine treatment is becoming increasingly accepted as monotherapy in low risk patients, we propose that radiotherapy should not be forgotten as an alternative which, with its attendant benefits of shorter duration and high compliance, may be more suitable for a number of patients.

Diagnosis of head-and-neck cancer from exhaled breath.

BACKGROUND: Head-and-neck cancer (HNC) is the eighth most common malignancy worldwide. It is often diagnosed late due to a lack of screening methods and overall cure is achieved in <50% of patients. Head-and-neck cancer sufferers often develop a second primary tumour that can affect the entire aero-digestive tract, mostly HNC or lung cancer (LC), making lifelong follow-up necessary. METHODS: Alveolar breath was collected from 87 volunteers (HNC and LC patients and healthy controls) in a cross-sectional clinical trial. The discriminative power of a tailor-made Nanoscale Artificial Nose (NA-NOSE) based on an array of five gold nanoparticle sensors was tested, using 62 breath samples. The NA-NOSE signals were analysed to detect statistically significant differences between the sub-populations using (i) principal component analysis with ANOVA and Student's t-test and (ii) support vector machines and cross-validation. The identification of NA-NOSE patterns was supported by comparative analysis of the chemical composition of the breath through gas chromatography in conjunction with mass spectrometry (GC-MS), using 40 breath samples. RESULTS: The NA-NOSE could clearly distinguish between (i) HNC patients and healthy controls, (ii) LC patients and healthy controls, and (iii) HNC and LC patients. The GC-MS analysis showed statistically significant differences in the chemical composition of the breath of the three groups. CONCLUSION: The presented results could lead to the development of a cost-effective, fast, and reliable method for the differential diagnosis of HNC that is based on breath testing with an NA-NOSE, with a future potential as screening tool.

The effect of a Radiology Conference consultation on cancer patients management.

BACKGROUND: The quantitative effect of consultation on cancer patient's management at a Radiology Conference was studied. PATIENTS AND METHODS: This prospective study included consecutive patients presented at the Radiology Conference of the Division of Oncology. Following the case presentation and discussion, the patient's oncologist completed a questionnaire which asked whether the consultation at the conference added new information regarding the patient's disease status, whether it influenced patient management and, if so, to what extent. RESULTS: Three hundred and eighty-three patients were included in the study. Significant new information was added for 189 (49%) patients and less consequential information was added for 134 (35%) patients. Major changes in management occurred in 143 (37%) patients after the Radiology Conference and minor changes were made in 56 (15%) patients. The influence of the cancer type on the rate of significant change in treatment and on the rate of major information addition was not statistically significant. CONCLUSION: Consultation at a Radiological Conference in a tertiary center led to major changes in the management of 37% of the cancer patients presented and provided important information regarding the patient's disease in up to 50% of patients.

Detection of lung, breast, colorectal, and prostate cancers from exhaled breath using a single array of nanosensors.

BACKGROUND: Tumour growth is accompanied by gene and/or protein changes that may lead to peroxidation of the cell membrane species and, hence, to the emission of volatile organic compounds (VOCs). In this study, we investigated the ability of a nanosensor array to discriminate between breath VOCs that characterise healthy states and the most widespread cancer states in the developed world: lung, breast, colorectal, and prostate cancers. METHODS: Exhaled alveolar breath was collected from 177 volunteers aged 20-75 years (patients with lung, colon, breast, and prostate cancers and healthy controls). Breath from cancerous subjects was collected before any treatment. The healthy population was healthy according to subjective patient's data. The breath of volunteers was examined by a tailor-made array of cross-reactive nanosensors based on organically functionalised gold nanoparticles and gas chromatography linked to the mass spectrometry technique (GC-MS). RESULTS: The results showed that the nanosensor array could differentiate between 'healthy' and 'cancerous' breath, and, furthermore, between the breath of patients having different cancer types. Moreover, the nanosensor array could distinguish between the breath patterns of different cancers in the same statistical analysis, irrespective of age, gender, lifestyle, and other confounding factors. The GC-MS results showed that each cancer could have a unique pattern of VOCs, when compared with healthy states, but not when compared with other cancer types. CONCLUSIONS: The reported results could lead to the development of an inexpensive, easy-to-use, portable, non-invasive tool that overcomes many of the deficiencies associated with the currently available diagnostic methods for cancer.

Immuno-chemotherapy in metastatic renal cell carcinoma: long-term results from the rambam and linn medical centers, Haifa, Israel.

Nephrectomy, immuno-chemotherapy and resection of residual disease have been the treatment of choice for patients with metastatic renal cell carcinoma during the past decades. The aim of this study was to report the long-term results of this treatment approach. Sixty-two patients with metastatic renal cell carcinoma participated in a Phase II study. At diagnosis, 32 patients had localized disease, 30 had metastatic disease and 53 underwent nephrectomy. Metastatic sites were lungs, lymph nodes, bones and liver. Immuno-chemotherapy consisted of: interleukin-2, interferon alpha, 5-fluorouracil and vinblastine. All patients were evaluated for toxicity and response to treatment. CR was achieved in 4 patients and PR in 14. Seven patients, with maximum response to immuno-chemotherapy underwent resection of residual tumor and reached CR. Therefore, CR was achieved in 11 patients (18%) with a median survival of +67 months. Flu-like symptoms were the common side effects. Performance status and histology type significantly affected survival. Nephrectomy, immuno-chemotherapy and resection of residual disease are recommended for patients with metastatic renal cell carcinoma.

Second primary tumors in mycosis fungoides patients: experience at the Northern Israel Oncology Center (1979-2002).

PURPOSE: Mycosis fungoides (MF) patients enjoy longstanding remissions following total skin electron irradiation (TSEI) but run the risk of developing secondary malignancies. Our purpose was to report our experience with the phenomenon of secondary malignancies in MF patients. PATIENTS AND METHODS: From 1979 to 2002, 84 patients with biopsy-proven MF were referred to our department for TSEI, using the modified Christie Hospital translational technique until 1992 and the Stanford technique after 1992. Median total dose was 32 Gy (range 16-44) Christie; 30 Gy (range 15-36) Stanford. Underdosed areas were boosted with a median total dose of 10-20 Gy. RESULTS: During a median follow-up of 73 months (range 2-191) from the end of the TSEI, 12 (15%) patients developed 17 second primary tumors within the irradiated areas and 6 patients developed 7 second primary tumors, either simultaneously with the newly diagnosed MF or prior to introduction of radiation therapy. CONCLUSION: The long-term prognosis was related solely to the second primary. Due to excellent long-lasting response rates following TSEI coupled with long-term survival, and the prognosis mainly associated to the stage and histology of the second malignancy, physicians should be aware of the possibility of second primary tumors.

[Cancer in Israel: mass mediated reality vs. real reality].

BACKGROUND: Cancer, being a terminal and often incurable disease, is a source of fear and concern for human beings. One of the most important sources of medical information in general, and cancer specifically, is the mass media. The media can shape beliefs regarding health and influence people's decision-making. The main hypothesis guiding this study, based on the theoretical framework of cultivation research, is that there will be considerable differences between media coverage and medical data regarding cancer in the Israeli population. METHOD: A systematic content analysis was applied to test this hypothesis, examining all the press reports (650 articles) published during the year 2000 in three of Israel's most popular daily newspapers--"Yedioth Ahronot", "Maariv" and "Haaretz". Data from the Israeli Ministry of Health was used for comparison with media reports to the population in terms of the types of cancer reported, the emphasis on death in the context of the disease, reports concerning treatment, and the age of cancer patients. RESULTS: The findings of the study are in accordance with the main hypothesis and show that the media's portrayal of cancer does not always reflect the medical reality regarding the above mentioned aspects. Several possible explanations are proposed in analyzing these findings, focusing mainly on the nature of news making and media selection, as well as on the impact of various interest groups such as pharmaceutical companies, hospitals. laboratories, oncology departments, and various organizations trying to promote awareness and raise funds for research. CONCLUSION: The findings of this study enhance a wide range of research in different areas of human knowledge that have documented processes of constructing "mass-mediated realities", but in the case of a fatal disease, the findings may have acute implications.

Primary lymphoma of the liver: clinical features and outcome of 9 patients.

PURPOSE: Primary liver lymphoma (PLL) is a rare lymphoproliferative disorder of unknown etiology. The prognosis in affected patients is poor, consisting of brief remissions, rapidly developing resistance to chemotherapy, early recurrence, and short survival. Most studies related to PLL are based on case reports. The aim of this retrospective study was to review our experience with PLL. PATIENTS AND METHODS: From 1985 to 2000, 9 patients who fulfilled the diagnostic criteria for PLL were treated at our hospital. All patients underwent a thorough work-up and were staged accordingly. RESULTS: The disease occured in middle and higher-aged patients (median age 63 years). Primary presenting complaints were abdominal pain, mainly in the right upper quadrant, and hepatomegaly. Liver function tests and lactate dehydrogenase (LDH) levels were elevated. Liver imaging (computed tomography-CT) and isotopic methods (gallium scan) demonstrated liver involvement either as solitary or multiple space-occupying lesions. Pathologic examination demonstrated diffuse, large cell (DLCL), B-type lymphoma in 7/9 (78%) patients. Doxorubicin-based chemotherapy was the mainstay of treatment. Good partial or complete remission rates were achieved in 7 patients, albeit for a brief period of time. CONCLUSION: Most patients with PLL succumb to their illness, despite its being relatively chemotherapy-sensitive. The introduction of intensive chemotherapy, plus/minus radiotherapy, and/or surgery has been considered in some studies.

Vinorelbine/VP-16 (etoposide) in metastatic breast cancer: a phase II study.

PURPOSE: This phase II study was conducted to evaluate the efficacy and tolerability of vinorelbine (navelbine) and oral VP-16 (etoposide) in pretreated metastatic breast cancer (MBC) patients. PATIENTS AND METHODS: Twenty-two female patients with therapy-resistant metastatic breast cancer were treated with vinorelbine 25 mg/m(2) i.v. on days 1 and 8 and oral VP-16 50 mg/m(2)/day for 14 days. Cycles were repeated every 28 days. Treatment was given until clear evidence of disease progression. RESULTS: Complete remission was observed in 3 (14%) patients, and partial remission or stable disease in 10 (45%) patients. Median duration of response was 4 months (range 2-8). Symptomatic improvement, irrespective of imaging methods results, as evaluated through improved performance status (PS), the lack of requirement for urgent palliative radiotherapy, and a decrease in steroids and analgesics doses was demonstrated in 10 (45%) patients through a special questionnaire completed by all patients. Side effects were manageable. Dose modification due to leucopenic fever were necessary in only 3 patients. Previous radiation therapy did not mitigate the application of full doses of chemotherapy. CONCLUSION: Vinorelbine/VP-16 combination is active and tolerable in relapsed and heavily pretreated MBC patients.

Prevalence and relevance of EBV latency in nasopharyngeal carcinoma in Israel.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is frequently associated with Epstein-Barr virus (EBV). The incidence of NPC in Western countries is lower than in the Far East, and EBV latency in NPC is less prevalent. Israel, as a part of the Mediterranean area, is one of the countries with an intermediate risk for NPC. METHODS: Immunohistochemistry (IHC) for latent membrane protein 1 (LMP-1) and in situ hybridisation (ISH) for EBV encoded RNA (EBER) were used to evaluate the prevalence and possible prognostic value of EBV latency among Israeli patients with NPC. Forty five patients with different NPC histologies were studied. RESULTS: LMP-1 IHC was positive in six samples only, all with undifferentiated histology. EBER ISH was positive in 40 of the 45 samples. According to histological type, three of five patients with squamous cell carcinoma were EBV positive and 37 of 40 non-keratinising and undifferentiated carcinoma cases were positive. Although EBV was more prevalent in patients with non-squamous carcinoma, the difference was not significant, probably because of the small number of patients with keratinising carcinoma. With regard to the clinical categories and survival, no significant difference could be detected between patients who were positive or negative for EBER ISH. No association was found between EBV latency and patient sex, age, origin, stage, or survival. CONCLUSIONS: NPC in Israel is highly associated with EBV latency as detected by EBER ISH. LMP-1 IHC is considerably less sensitive in detecting EBV latency in NPC among the same patient group.

Expression of HER2 and C-KIT in nasopharyngeal carcinoma: implications for a new therapeutic approach.

We sought to determine the expression and prognostic significance of HER2 and c-KIT proteins in nasopharyngeal carcinoma (NPC). In this retrospective study, immunohistochemical stains for HER2 and c-KIT were performed on formalin-fixed paraffin-embedded sections from 49 patients with NPC who were treated at our hospital from 1971 to 2000. The clinical and immunohistochemical data were correlated, including gender, ethnic origin, age, histological type, EBV status (EBER in situ hybridization), stage, and overall survival. HER2 expression was not found in the tested samples. C-KIT overexpression was found in 33% (16/49) of the patients. Nine of the 16 samples (56%) were strongly positive for c-KIT protein (staining of >50% of the tumor cells). C-KIT expression was associated with younger age. C-KIT was not found in patients with squamous carcinoma or in those with negative EBV status, although these two groups consisted of only five patients each. Although c-KIT-positive cases tended to be associated with slightly better survival, this was not statistically significant. C-KIT protein was expressed in one third of the NPC patients in this study, only in EBV-positive, undifferentiated, or nonkeratinizing carcinoma patients. Further study is needed to check whether c-KIT expression is correlated with c-KIT DNA mutations and to test the possibility of treatment with imatinib mesylate (Gleevec). HER2 protein was negative in the same tested specimens.

Primary lymphoma of bone--a retrospective study. Experience at the Northern Israel Oncology Center (1979-2000).

OBJECTIVE: This retrospective study describes our experience with the diagnosis, treatment, results and long-term follow-up of primary bone lymphoma (PBL). PATIENTS AND METHODS: Nineteen patients diagnosed with PBL were reviewed. Seven patients presented with stage I(E) disease, four with stage II(E) (regional lymphadenopathy), and eight with stage IV disease (disseminated bone involvement). Only one stage IV patient exhibited 'B' symptoms. The majority (72%) demonstrated diffuse, large cell, B-type lymphoma. All patients were treated with adriamycin-based chemotherapy and consolidation radiotherapy to the primary site (8 patients: early PBL) or the most bulky area (3 patients: stage IV PBL). RESULTS: Ten stage I(E)/II(E) patients are alive with no evidence of disease (NED) and only one died due to metastatic secondary lung cancer while with NED from his PBL. Eight stage IV patients are alive with NED. Median follow-up for all living patients: 77 months. Side effects were mild and did not necessitate delay in treatment. CONCLUSIONS: Our departmental policy of treating PBL patients with an anthracycline-based regimen and involved field radiotherapy proved to be successful in achieving excellent long-term, disease-free survival. Phase III randomized, controlled, clinical trials will determine the true role of consolidation radiotherapy in PBL, when considering severe late side effects, including radiation-induced bone tumors.