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).

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.

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.

Neoadjuvant radiotherapy concurrent with weekly paclitaxel and carboplatin and followed by surgery in locally advanced non-small-cell lung cancer.

Thirty-seven patients were enrolled in a phase II study to evaluate the efficacy and toxicity of neoadjuvant radiotherapy concurrent with weekly paclitaxel and carboplatin in locoregionally advanced non-small-cell lung cancer (NSCLC). The study was also designed to evaluate the operability following concurrent chemoirradiation. The following response rates to chemoirradiation were obtained: complete response (CR) 5 of 37 (13.5%), partial response 14 of 37 (38%), stable disease 12 of 37 (32.5%) and PD 6 of 37 (16%). Twenty patients underwent surgery, and in 19 patients the tumor was totally resected. There was pathologic CR in 4 patients. Moderate/severe esophagitis developed in 16 patients (43%); hematologic toxicity was mild. There was one case of postoperative mortality. Nine patients are alive without evidence of disease at 5+ to 39+ months. Median survival is 22 months. It is concluded that neoadjuvant radiotherapy concurrent with weekly paclitaxel/carboplatin is effective and well tolerated in patients and feasible for patients with locally advanced NSCLC, allowing complete tumor resection in 56% of the cases.