Does a homeopathic medicine reduce hot flushes induced by adjuvant endocrine therapy in localized breast cancer patients? A multicenter randomized placebo-controlled phase III trial.

PURPOSE: Endocrine therapy (ET) used to reduce the risk of recurrence in hormone receptor-expressing disease (75% of breast cancers) is associated with worsening of climacteric symptoms with a negative impact on quality of life (QoL). Homeopathy might allow a better management of hot flushes (HF). METHODS: In this multicenter randomized double-blind placebo-controlled phase III study ( ClinicalTrials.gov NCT01246427), we enrolled ≥ 18 years old women with histologically proven non metastatic localized breast cancer, with Eastern Cooperative Oncology Group-Performance Status (ECOG-PS) ≤ 1, treated for at least 1 month with adjuvant ET, and complaining about moderate to severe HF. Patients should not be scheduled for chemotherapy or radiotherapy, and had no associated pathology known to induce HF. After a 2- to 4-week placebo administration, we randomly assigned (1:1) patients with HFS ≥ 10 using an interactive web-based centralized platform to BRN-01 homeopathic medicine complex (Actheane®) in arm A or Placebo (Arm P). Randomization was stratified by adjuvant ET (taxoxifen/aromatase inhibitor) and recruiting site. HF scores (HFS) were calculated as the mean of HF frequencies before randomization, at 4, and at 8 weeks post-randomization (pre-, 4w,- and 8w-) weighted by a 4-level intensity scale. Primary endpoint was assessed at 4-week post-randomization, as the variation between pre- and 4w-HFS. Secondary endpoints included HFS variation between pre- and 8w-HFS, compliance and tolerance assessed 8 weeks after randomization, and QoL and satisfaction assessed at 4- and 8-week post-randomization. RESULTS: Two hundred ninety-nine patients were included, and 138 (46.2%) randomized (A, 65; P, 73). Median 4w-HFS absolute variation (A, - 2.9; P, - 2.5 points, p = 0.756) and relative decrease (A, - 17%; P, - 15%, p = 0.629) were not statistically different. However, 4w-HFS decreased for 46 (75%) in A vs 48 (68%) patients in P arm. 4w-QoL was stable or improved for respectively 43 (72%) vs 51 (74%) patients (p = 0.470). CONCLUSIONS: The efficacy endpoint was not reached, and BRN-01 administration was not demonstrated as an efficient treatment to alleviate HF symptoms due to adjuvant ET in breast cancer patients. However, the study drug administration led to decreased HFS with a positive impact on QoL. Without any recommended treatment to treat or alleviate the HF-related disabling symptoms, Actheane® could be a promising option, providing an interesting support for better adherence to ET, thereby reducing the risk of recurrence with a good tolerance profile.

Impact of distance from surgery department on the outcome of patients followed for non-small-cell lung cancer in the respiratory department of nonacademic hospitals: Results of the KBP-2010-study.

OBJECTIVE: Increased postoperative mortality in low volume centers has contributed to merge and space thoracic surgical centers. Some studies have showed that the likelihood of receiving surgery was lower in lung cancer patients living far from a thoracic surgery center. Our objective was thus to determine whether surgery and survival rates in patients with non-small-cell lung cancer (NSCLC) were influenced by the distance between the respiratory and thoracic surgery departments. METHODS: KBP-2010-CPHG is a prospective multicenter epidemiological study including 6083 patients followed in 104 nonacademic hospitals for primary NSCLC diagnosed in 2010. Distance between respiratory and thoracic surgery departments were obtained retrospectively. Predictive factors for surgery and mortality were identified by logistic regression and Cox hazard model. RESULTS: Twenty-three percent of hospitals had a thoracic surgery department; otherwise, mean distance between the hospital and the surgery center was 65km. Nineteen percent of patients underwent surgery. Distance was neither an independent factor for surgery (odds-ratios [95% CI]: 0.971 [0.74-1.274], 0.883 [0.662-1.178], and 1.015 [0.783-1.317] for 1-34, 35-79, and ≥80km vs. 0km) nor for mortality (hazard-ratios [95% CI]: 1.020 [0.935-1.111], 1.003 [0.915-1.099], and 1.006 [0.927-1.091]) (P>0.05). DISCUSSION: This result supports the French national strategy which merges surgery departments and should reassure patients (and physicians) who could be afraid to be lately addressed to surgery or loose chance when being followed far from the thoracic surgical center.

No impact of passive smoke on the somatic profile of lung cancers in never-smokers.

EGFR and HER2 mutations and ALK rearrangement are known to be related to lung cancer in never-smokers, while KRAS, BRAF and PIK3CA mutations are typically observed among smokers. There is still debate surrounding whether never-smokers exposed to passive smoke exhibit a "smoker-like" somatic profile compared with unexposed never-smokers. Passive smoke exposure was assessed in the French BioCAST/IFCT-1002 never-smoker lung cancer cohort and routine molecular profiles analyses were compiled. Of the 384 patients recruited into BioCAST, 319 were tested for at least one biomarker and provided data relating to passive smoking. Overall, 219 (66%) reported having been exposed to passive smoking. No significant difference was observed between mutation frequency and passive smoke exposure (EGFR mutation: 46% in never exposed versus 41% in ever exposed; KRAS: 7% versus 7%; ALK: 13% versus 11%; HER2: 4% versus 5%; BRAF: 6% versus 5%; PIK3CA: 4% versus 2%). We observed a nonsignificant trend for a negative association between EGFR mutation and cumulative duration of passive smoke exposure. No association was found for other biomarkers. There is no clear association between passive smoke exposure and somatic profile in lifelong, never-smoker lung cancer.

Noninvasive diagnosis of actionable mutations by deep sequencing of circulating free DNA in lung cancer from never-smokers: a proof-of-concept study from BioCAST/IFCT-1002.

PURPOSE: Tumor somatic mutation analysis is part of the standard management of metastatic lung cancer. However, physicians often have to deal with small biopsies and consequently with challenging mutation testing. Circulating free DNA (cfDNA) is a promising tool for accessing the tumor genome as a liquid biopsy. Here, we evaluated next-generation sequencing (NGS) on cfDNA samples obtained from a consecutive series of patients for the screening of a range of clinically relevant mutations. EXPERIMENTAL DESIGN: A total of 107 plasma samples were collected from the BioCAST/IFCT-1002 lung cancer study (never-smokers cohort). Matched tumor DNA (tDNA) was obtained for 68 cases. Multiplex PCR-based assays were designed to target specific coding regions in EGFR, KRAS, BRAF, ERBB2, and PI3KCA genes, and amplicon sequencing was performed at deep coverage on the cfDNA/tDNA pairs using the NGS IonTorrent Personal Genome Machine Platform. RESULTS: CfDNA concentration in plasma was significantly associated with both stage and number of metastatic sites. In tDNA, 50 mutations (36 EGFR, 5 ERBB2, 4 KRAS, 3 BRAF, and 2 PIK3CA) were identified, of which 26 were detected in cfDNA. Sensitivity of the test was 58% (95% confidence interval, 43%-71%) and the estimated specificity was 87% (62%-96%). CONCLUSION: These data demonstrate the feasibility and potential utility of mutation screening in cfDNA using IonTorrent NGS for the detection of a range of tumor biomarkers in patients with metastatic lung cancer.

Sequential use of bronchial aspirates, biopsies and washings in the preoperative management of lung cancers.

BACKGROUND: The combination of cytology and biopsies improves the recognition and typing of small cell (SCLC) versus non small cell (NSCLC) lung cancers in the fiberoptic bronchoscopy assessment of centrally located tumours. METHODS: We studied whether bronchial aspirates performed before biopsies (BA) and washings performed after biopsies (BW) could increase the diagnostic yield of fiberoptic bronchoscopy. A series of 334 consecutive samples taken in patients with suspicious fiberoptic bronchoscopy findings was studied. Two hundred primary tumours were included in the study. The actual diagnosis was based on surgical tissue specimen analysis and/or imaging techniques. The typing used was that of the 1999 WHO/IASLC classification. RESULTS: The diagnosis of malignancy and tumour typing were analyzed according to the sequential (combined) or single use of tests. Malignancy was assessed by cytology in 144/164 (87.8%) positive biopsy cases and in 174/200 tumour cases (87.0%). BA before biopsies allowed 84.0% of cancers to be diagnosed, whereas BW after biopsies allowed 79.0% of cancers to be found (p = ns). However, combining biopsies with BW allowed 94.0% of cancers to be diagnosed, whereas 82.0% were diagnosed by biopsies alone (p < 0.001). The highest diagnostic yield was obtained with the combination of BA, biopsies and BW, with 97.0% sensitivity. Exact concordance in typing was obtained in 83.8% of cases. The six surgically resected cases (3.0%) with negative cytology and biopsy results included four squamous cell carcinomas with necrotizing or fibrous surface and two adenocarcinomas, pT1 stage. CONCLUSION: Fiberoptic bronchoscopy may reach a yield of close to 100% in the diagnosis and typing of centrally located, primary lung cancers by combining bronchial aspirates, biopsies and washings.