Updated results from the phase 3 HELIOS study of ibrutinib, bendamustine, and rituximab in relapsed chronic lymphocytic leukemia/small lymphocytic lymphoma.

We report follow-up results from the randomized, placebo-controlled, phase 3 HELIOS trial of ibrutinib+bendamustine and rituximab (BR) for previously treated chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) without deletion 17p. Overall, 578 patients were randomized 1:1 to either ibrutinib (420 mg daily) or placebo, in combination with 6 cycles of BR, followed by ibrutinib or placebo alone. Median follow-up was 34.8 months (range: 0.1-45.8). Investigator-assessed median progression-free survival (PFS) was not reached for ibrutinib+BR, versus 14.3 months for placebo+BR (hazard ratio [HR] [95% CI], 0.206 [0.159-0.265]; P < 0.0001); 36-month PFS rates were 68.0% versus 13.9%, respectively. The results are consistent with the primary analysis findings (HR = 0.203, as assessed by independent review committee, with 17-month median follow-up). Median overall survival was not reached in either arm; HR (95% CI) for ibrutinib+BR versus placebo: 0.652 (0.454-0.935; P = 0.019). Minimal residual disease (MRD)-negative response rates were 26.3% for ibrutinib+BR and 6.2% for placebo+BR (P < 0.0001). Incidence of treatment-emergent adverse events (including grades 3-4) were generally consistent with the initial HELIOS report. These long-term data support improved survival outcomes and deepening responses with ibrutinib+BR compared with BR in relapsed CLL/SLL.

Autologous stem cell transplantation for patients aged 60 years or older with refractory or relapsed classical Hodgkin's lymphoma: a retrospective analysis from the French Society of Bone Marrow Transplantation and Cell Therapies (SFGM-TC).

This report retrospectively analyzed the outcome of 91 patients aged 60 years or older with refractory/relapsed (R/R) classical Hodgkin's lymphoma (cHL) who underwent autologous stem cell transplantation (ASCT) between 1992 and 2013 and were reported to the French Society of Bone Marrow Transplantation and Cell Therapies registry. The median age at transplant was 63 years. The majority of patients exhibited disease chemosensitivity to salvage treatment (57 complete responses, 30 partial responses, 1 progressive disease and 3 unknown). The most frequent conditioning regimen consisted of BCNU, cytarabine, etoposide, melphalan (BEAM) chemotherapy (93%). With a median follow-up of 54 months, 5-year estimates of overall survival (OS) and progression free survival (PFS) for the entire group were 67 and 54%, respectively. Despite the missing data, in univariate analysis, the number of salvage chemotherapy lines (1-2 versus ⩾3) significantly influenced the OS, unlike the other prognostic factors (stage III-IV at relapse, disease status before ASCT and negative positron emission tomography (PET) scan) encountered in younger patients. In spite of its limitations, this retrospective study with a long-term follow-up suggests that ASCT is a valid treatment option for chemosensitive R/R cHL in selected elderly patients, with an acceptable rate of toxicity.

Ofatumumab in refractory chronic lymphocytic leukemia: experience through the French early access program.

BACKGROUND: The Autorisation Temporaire d'Utilisation (ATU) is an early access program available in France for drugs aimed at treating severe diseases not yet covered by a marketing authorization, for patients without any other therapeutic option and who cannot be included in a clinical trial. PATIENTS AND METHODS: This report presents the use of single-agent ofatumumab in 30 patients with advanced chronic lymphocytic leukemia (CLL) in the French ATU program. RESULTS: These very-high-risk patients had received multiple previous treatments (median = 6), and most had disease that was fludarabine-refractory or alemtuzumab-refractory (or both) or was unsuitable for alemtuzumab treatment. In the intent-to-treat analysis, the overall response rate was 47% (4 of 30, complete response; 10 of 30, partial response). Of 13 patients with 17p deletion, 6 displayed response to ofatumumab, including 2 complete responses. Treatment was well tolerated, with 17 grade 3 or 4 adverse events; 4 cases of grade 3 or 4 infusion reactions were reported, with favorable immediate outcome. Among nonhematologic complications, infections were the most frequent. CONCLUSION: The results confirm the efficacy and acceptable tolerability profile of ofatumumab as a single agent in severely ill patients with CLL. Attention should be paid to possible early infusion reactions to ofatumumab, as well as to the risk of infection.

Combination of gemcitabine and doxorubicin in rapidly progressive metastatic renal cell carcinoma and/or sarcomatoid renal cell carcinoma.

BACKGROUND/AIMS: Metastatic renal cell carcinoma (mRCC) can be rapidly progressive when tumors exhibit sarcomatoid or Fuhrman grade 4 features. Efficacy of gemcitabine (Gem) with doxorubicin (Dox) in sarcomatoid or rapidly progressive mRCC has been reported. We retrospectively evaluated Gem + Dox in a consecutive cohort of this particular patient population. PATIENTS AND METHODS: Patients had an Eastern Cooperative Oncology Group performance status of 2 or more and rapidly progressive mRCC or mRCC with sarcomatoid features. Gem (1,500 mg/m(2)) and Dox (50 mg/m(2)) were given every 2 weeks with granulocyte colony-stimulating factor. RESULTS: Twenty-nine patients were treated. Sarcomatoid features were predominant in 6 patients, while 14 tumors were Fuhrman grade 4. All patients had progressive mRCC within 4 months. No grade 4 toxicity or drug-related death was reported. One partial response (7 months), 1 mixed response, and 14 stable diseases (≥4 months for 9 patients) were observed and no response was seen in sarcomatoid tumors. The median disease-free survival was 3.7 months (≥6 months for 8 patients) and the median overall survival was 4.8 months (>12 months for 5 patients). CONCLUSION: This study showed a lower response rate than previously reported. Nevertheless, some patients had prolonged survival outcomes. This combination could be an option in sarcomatoid histology (NCCN guidelines) or rapidly progressive disease, but this population represents an unmet medical need.

[Using medical imaging for a comprehensive breast cancer screening program]. / Imagerie au service du dépistage : l'exemple du dépistage organisé du cancer du sein.

We described here the national breast cancer-screening program that is used, in France, today. First we depict official rules and regulations along with the organization needed to screen a whole population. Then, a technical assessment is made on the efficacy and limits on mammography analyses leading to tumor classification. Finally, an evaluation of the program is discussed.

[Assessment of the dense breast within the French screening program: the role of ultrasonography]. / Seins denses et dépistage organisé: place de l'échographie.

Mammographic density is associated with an increased risk of breast cancer. It also reduces the reliability of screening mammography. Among the population targeted by the French screening program, about 28% have dense breasts and 3% have very dense breasts. Breast density varies with age, HRT and mammographic technique. Ultrasonography for dense but otherwise clinically and mammographically normal breasts allows detection of cancers not visible on mammograms. The French program protocol allows the evaluation of results from breast US in this context with regards to the number of detected cancers and false positive rate.

[Bilateral ductal carcinoma in situ of the breast: independent events or bilateral disease?]. / Carcinomes canalaires in situ bilatéraux: événements indépendants ou maladie bilatérale?

OBJECTIVES: In a retrospective study of bilateral Ductal Carcinoma In Situ (DCIS), cases were analysed to determine the relationship between the two events. MATERIAL AND METHODS: From 1971 to 2001, among 812 patients with DCIS in Bergonie Institute, 78 suffering from bilateral DCIS and only19 were treated entirely in our institute. It was either synchronous DCIS or asynchronous (before 6 months). We realised a comparative study between, clinical and pathological characteristics of each DCIS. RESULTS: In case of asynchronous DCIS, contra lateral DCIS occurred after a median 75-months period and until 22 years after the first event. We found at least for one histological subtype an agreement in 53% of cases. In 31% of cases, the grade was the same. For low plus intermediary grade versus high grade, the agreement was 53%. There was a subtype and grade agreement of 32% and a subtype or grade agreement in 63% of cases. CONCLUSION: Histological agreement between the two lesions indicated the possible existence of in situ bilateral disease in these women. The local relapse rate was 20% and all of them were invasive. The risk of relapse in controlateral breast is high and patient needs a long follow up even in case of mastectomy.

PET scans for decision-making in metastatic renal cell carcinoma: a single-institution evaluation.

OBJECTIVE: Therapeutic decision-making in metastatic renal cell carcinoma (MRCC) is based on conventional radiological evaluation. Fluorodeoxyglucose positron emission tomography (FDG-PET) scans may modify this strategy. METHODS: Patients with MRCC for whom a therapeutic decision had been made underwent an FDG-PET scan in order to complete the standard radiological evaluation. RESULTS: Twenty-four patients and 26 FDG-PET scans were eligible. In 18 patients, metastatic disease was evaluable on the computed tomography (CT) scan; the FDG-PET scan was positive in 16 patients and negative in 10. In 2 patients, the FDG-PET scan was positive while they were considered disease free on radiological evaluation. In 5 patients (20.8%), the previous therapeutic decision was changed. Thirteen patients had a pathological evaluation for 19 sites. One patient out of 13 had a false-positive FDG-PET scan, while 4 sites out of 6 were false-negative. The sensitivity was 75% (95% CI: 47.6-92.7) and the predictive positive value was 92.3% (95% CI: 64-99.8). With a median follow-up of 24 months, 3 patients developed new metastatic sites. CONCLUSION: Our data suggest that, when positive, an FDG-PET scan may modify the decision made; when negative, it should not modify decision-making especially for surgery, owing to its sensitivity.

[Psychological adjustment of stereotactic breast biopsy instrumentation procedures: about 73 cases]. / Le vécu psychologique de la procédure de prélèvements percutanés du sein. Etude quasi prospective à propos de 73 cas.

OBJECTIVE: The aim of the study was to investigate patients' perceptions after stereotactic breast biopsy instrumentation, after both procedure and results. PATIENTS AND METHOD: From 1 March 2002 to 31 March 2003, a questionnaire (Likert response type) on stress was given to 73 patients who had breast biopsies procedures, the first time at the end of the procedure (T1) and then after the histological diagnosis (T2). RESULTS: The questionnaire was validated through analysis of principal component with Varimax rotation. Three factors were identified: procedure, quality of life, information and perception after biopsy. Responses were analysed with Chi-square. Two groups of women were identified, the first group (G1) corresponding to patients with a benign diagnosis (N=32) and the second group (G2) to patients with malignant diagnosis (N=32). Only the "procedure" factor was different at T1 and T2 (P=0.022). Compression was found to be painful: 11% at T1 versus 21% at T2. Women were disturbed by local anesthesia: 26% at T1 versus 21% at T2. Biopsy was painful: 6% at T1 versus 13% at T2. Examination was too long: 24% at T1 versus 35% at T2. The procedure was discomfortable: 52% at T1 versus 54% at T2. Information satisfied patients in 90% cases. There was no statistically significant difference according to procedures and histological disease (P=0.357). DISCUSSION AND CONCLUSION: Information and medical empathy conditioned patients' perceptions. Patients tolerated the procedures well.

[Breast cancer screening: specific features of the French program]. / Le dépistage organisé des cancers du sein: particularités du système français.

The breast cancer screening program developed in France is an original model, adapted to the specific features of the French healthcare system. Both public and private mammographic units are involved with an active participation of practitioners in prescription and management. Two views per breast every two years together with physical examination are performed. An immediate diagnosis process is planned if an abnormality is detected. The French model is also a rigorous public health program involving prior training, strict organisation, quality assurance of all the process, double reading and epidemiologic evaluation. Logical benefits and difficulties of such a system are discussed.

[Psychological adjustment of short interval follow-up mammography: about 50 cases]. / Une étude exploratoire sur le vécu psychologique des femmes lors de la surveillance des anomalies mammographiques probablement bénignes: à propos de 50 cas.

The objective was to investigate women's perceptions and the perceived stress experience when undergoing surveillance mammography for benign lesions (ACR3, BI-RADS). A semi-prospective study was carried out on women with diagnosed "probably benign" breast abnormalities. It was a multicentric study from 1st March to 10th June 2002. The survey was performed at the first follow-up mammography and included questions about perceptions and perceived stress related to the follow-up experience. The response is analysed with chi-square test. Fifty women (35-75 years) answered the questionnaire. All women were satisfied with reception. The mammographies were painful (23 cases). Subsequent time seemed to be too long (seven cases) and they were anxious in 19 cases. Quality of life was spoiled (disturbed) (20 cases). Professional and social perturbations were not frequent (four cases). Speaking to a relative is frequent (39 cases), but patients were not satisfied with it (33 cases). Medical information was estimated (47 cases) but was not satisfactory (36 cases). The median of the stress scale is 4-5. There are two pickaxes, one at 2 (11 cases), the second at 5 (8 cases). "Low-stressed" women could have an avoidance coping. "High-stressed" women could use a helplessness- hopelessness coping strategy. Women reported a good and informative medical support and adequate comprehension of the short follow-up mammography. They were reassured by the medical care, but the evaluation of the stress level shows it to be high, probably due to the uncertainty of diagnosis.

[Breast biopsies: stereotactic vacuum-assisted core biopsy and stereotactic surgical breast biopsy]. / Les prélèvements mammaires en stéréotaxie: macrobiopsies avec aspiration et biopsies chirurgicales stéréotaxiques.

Stereotactically-guided procedures for diagnosis of breast lesions can avoid a lot of surgical biopsies. Stereotactic guidance is used for vacuum-assisted core biopsies and for stereotactic breast biopsies. Technical details of the procedures are described, and the benefits and the limits of these methods are discussed. Indications for breast sampling are proposed according to the Breast Imaging Reporting and Data System (BI-RADS) assessment categories.

["Standards, Options and Recommendations 2001" for radiotherapy in patients with non-metastatic infiltrating breast cancer. Update. National Federation of Cancer Campaign Centers (FNCLCC)]. / Standards, Options et Recommandations 2001 pour la radiothérapie des patientes atteintes d'un cancer du sein infiltrant non métastatique, mise à jour. Fédération nationale des centres de lutte contre le cancer (FNCLCC).

CONTEXT: The "Standards, Options and Recommendations" (SOR) project, started in 1993, is a collaboration between the Federation of french cancer centers (FNCLCC), the 20 french cancer centers, and specialists from french public universities, general hospitals and private clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and the outcome of cancer patients. The methodology is based on a literature review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery. OBJECTIVES: To develop clinical practice guidelines for non metastatic breast cancer patients according to the definitions of the Standards, Options and Recommendations project. METHODS: Data were identified by searching Medline, web sites, and using the personal reference lists of members of the expert groups. Once the guidelines were defined, the document was submitted for review to 148 independent reviewers. RESULTS: This article presents the chapter radiotherapy resulting from the 2001 update of the version first published in 1996. The modified 2001 version of the standards, options and recommendations takes into account new information published. The main recommendations are: (1) Breast irradiation after conservative surgery significantly decrease the risk of local recurrence (level of evidence A) and the decrease in the risk of local recidive after chest wall irradiation is greater as the number of risk factors for local recurrence increases (level of evidence A). (2) After conservative surgery, a whole breast irradiation should be performed at a minimum dose of 50 Gy in 25 fractions (standard, level of evidence A). (3) A boost in the tumour bed should be performed in women under 50 years, even if the surgical margins are free (standard, level of evidence B). (4) Internal mammary chain irradiation is indicated for internal or central tumours in the absence of axillary lymph node involvement (expert agreement) and in the presence of lymph node involvement (standard, level of evidence B1). (5) Sub- and supra-claviculr lymph node irradiation is indicated in patients with axillary node involvement (standard, level of evidence B1).