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Concept: Response rate


Background Bruton’s tyrosine kinase (BTK) is a mediator of the B-cell-receptor signaling pathway implicated in the pathogenesis of B-cell cancers. In a phase 1 study, ibrutinib, a BTK inhibitor, showed antitumor activity in several types of non-Hodgkin’s lymphoma, including mantle-cell lymphoma. Methods In this phase 2 study, we investigated oral ibrutinib, at a daily dose of 560 mg, in 111 patients with relapsed or refractory mantle-cell lymphoma. Patients were enrolled into two groups: those who had previously received at least 2 cycles of bortezomib therapy and those who had received less than 2 complete cycles of bortezomib or had received no prior bortezomib therapy. The primary end point was the overall response rate. Secondary end points were duration of response, progression-free survival, overall survival, and safety. Results The median age was 68 years, and 86% of patients had intermediate-risk or high-risk mantle-cell lymphoma according to clinical prognostic factors. Patients had received a median of three prior therapies. The most common treatment-related adverse events were mild or moderate diarrhea, fatigue, and nausea. Grade 3 or higher hematologic events were infrequent and included neutropenia (in 16% of patients), thrombocytopenia (in 11%), and anemia (in 10%). A response rate of 68% (75 patients) was observed, with a complete response rate of 21% and a partial response rate of 47%; prior treatment with bortezomib had no effect on the response rate. With an estimated median follow-up of 15.3 months, the estimated median response duration was 17.5 months (95% confidence interval [CI], 15.8 to not reached), the estimated median progression-free survival was 13.9 months (95% CI, 7.0 to not reached), and the median overall survival was not reached. The estimated rate of overall survival was 58% at 18 months. Conclusions Ibrutinib shows durable single-agent efficacy in relapsed or refractory mantle-cell lymphoma. (Funded by Pharmacyclics and others; number, NCT01236391 .).

Concepts: Cancer, Signal transduction, Response rate, Chemotherapy, Protein kinase, Tyrosine kinase, Lymphoma, Blood disorders


Background In a phase 1 trial, axicabtagene ciloleucel (axi-cel), an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, showed efficacy in patients with refractory large B-cell lymphoma after the failure of conventional therapy. Methods In this multicenter, phase 2 trial, we enrolled 111 patients with diffuse large B-cell lymphoma, primary mediastinal B-cell lymphoma, or transformed follicular lymphoma who had refractory disease despite undergoing recommended prior therapy. Patients received a target dose of 2×106 anti-CD19 CAR T cells per kilogram of body weight after receiving a conditioning regimen of low-dose cyclophosphamide and fludarabine. The primary end point was the rate of objective response (calculated as the combined rates of complete response and partial response). Secondary end points included overall survival, safety, and biomarker assessments. Results Among the 111 patients who were enrolled, axi-cel was successfully manufactured for 110 (99%) and administered to 101 (91%). The objective response rate was 82%, and the complete response rate was 54%.With a median follow-up of 15.4 months, 42% of the patients continued to have a response, with 40% continuing to have a complete response. The overall rate of survival at 18 months was 52%. The most common adverse events of grade 3 or higher during treatment were neutropenia (in 78% of the patients), anemia (in 43%), and thrombocytopenia (in 38%). Grade 3 or higher cytokine release syndrome and neurologic events occurred in 13% and 28% of the patients, respectively. Three of the patients died during treatment. Higher CAR T-cell levels in blood were associated with response. Conclusions In this multicenter study, patients with refractory large B-cell lymphoma who received CAR T-cell therapy with axi-cel had high levels of durable response, with a safety profile that included myelosuppression, the cytokine release syndrome, and neurologic events. (Funded by Kite Pharma and the Leukemia and Lymphoma Society Therapy Acceleration Program; ZUMA-1 number, NCT02348216 .).

Concepts: Medicine, Cancer, Response rate, B cell, Types of cancer, Lymphoma, Thymus, Follicular lymphoma


Patients with cutaneous melanoma metastases have experienced excellent responses to intralesional interleukin (IL)-2. This has led to its recent inclusion into the US National Comprehensive Cancer Network guidelines for management of cutaneous melanoma metastases. Despite this, intralesional IL-2 has not been highlighted in the US literature nor have US physicians adopted it.

Concepts: Cancer, Breast cancer, Metastasis, Lung cancer, Response rate, Chemotherapy, Melanoma, Basal cell carcinoma


The HCAHPS Survey obtains hospital patients' experiences using four modes: Mail Only, Phone Only, Mixed (mail/phone follow-up), and Touch-Tone (push-button) Interactive Voice Response with option to transfer to live interviewer (TT-IVR/Phone). A new randomized experiment examines two less expensive modes: Web/Mail (mail invitation to participate by Web or request a mail survey) and Speech-Enabled IVR (SE-IVR/Phone; speaking to a voice recognition system; optional transfer to an interviewer). Web/Mail had a 12% response rate (vs. 32% for Mail Only and 33% for SE-IVR/Phone); Web/Mail respondents were more educated and less often Black than Mail Only respondents. SE-IVR/Phone respondents (who usually switched to an interviewer) were less often older than 75 years, more often English-preferring, and reported better care than Mail Only respondents. Concerns regarding inconsistencies across implementations, low adherence to primary modes, or low response rate may limit the applicability of the SE-IVR/Phone and Web/Mail modes in HCAHPS and similar standardized environments.

Concepts: Response rate, Hospital, Randomization, Speech recognition, Interactive voice response, User interface techniques


Autologous stem cell transplantation (ASCT) is considered as an attractive treatment option for young mantle cell lymphoma (MCL) patients. This retrospective SFGM-TC study analyzed the outcome of 500 MCL patients treated with ASCT and investigated parameters that may modify the outcome of patients who proceeded to ASCT upfront (n = 396). For all patients, median age at ASCT was 56 years (range, 26-71). Median follow-up was 34 months. Three-year progression free survival (PFS) and overall survival (OS) were 63.5 % [95 % CI, 58.7-68.6 %] and 79.5 % [95 % CI, 75.3-83.4 %], respectively. Median time from ASCT to relapse was 22 months (range, 0-136 m). For patients transplanted upfront and in multivariate analysis, age (HR = 2 [1.2-3.4], p = .01, and HR = 2.3 [1.2-4.5], p = .01), disease status at time of ASCT (HR = 1.7 [1.1-2.6], p = .01 and HR = 1.8 [1.1-3.1], p = .03), and use of rituximab (HR = 0.5 [0.3-0.8], p = .002 and HR = 0.5 [0.3-0.9], p = .01) were statistically predictive for both PFS and OS. Also, first line treatment including anthracycline and high-dose cytarabine followed by ASCT conditioned with TAM improved PFS. To conclude, this study suggests that ASCT in MCL can provide a high response rate but may not be sufficient to cure MCL even when ASCT is performed upfront, highlighting the need for innovative approaches before ASCT, aiming to increase complete response rate, and after ASCT, to maintain response.

Concepts: Response rate, Chemotherapy, Median, Multivariate statistics, Organ transplant, Mantle cell lymphoma, Mantle zone


BACKGROUND: Preoperative treatment is a promising strategy for improving long-term outcomes in advanced esophageal cancer. Two tumor response evaluation criteria for preoperative treatment are available: response evaluation criteria in solid tumors (RECIST) and histological criteria. This prospective study aimed to identify which was a better surrogate end point for survival in the preoperative setting. METHODS: We analyzed all eligible patients (n = 164) from the preoperative treatment group in a phase III trial comparing preoperative versus postoperative 5-fluorouracil plus cisplatin for clinical stage II or III esophageal cancer. Intercriteria reliability was evaluated with the proportion of agreement and the kappa coefficient. For validity analyses, hazard ratios (HR) of response to nonresponse and differences in response rates between short- and long-term survivors were evaluated. RESULTS: The clinical and histological response rates were 37.8 % (62 of 164) and 20.1 % (33 of 164), respectively. The proportion of agreement for response to nonresponse between the 2 criteria was 70.3 %, and the kappa coefficient was 0.34. The HR for death in patients with histological response (0.22, 95 % confidence interval 0.09-0.55, P < 0.001) was lower than for those with RECIST response (0.55, 95 % confidence interval 0.33-0.91, P = 0.018). The difference in response rates between short- and long-term survivors according to histological criteria (27 vs. 7 %, P < 0.001) was larger than with RECIST (42 vs. 30 %, P = 0.13). CONCLUSIONS: Intercriteria agreement was relatively low, and histological criteria yielded more valid assessments of response than RECIST. Histological response rate seemed to be the better surrogate end point of survival in the preoperative setting.

Concepts: Cancer, Oncology, Cancer staging, Medical terms, Response rate, Tumor, Neoplasm, Esophageal cancer


Quality of life is a complex construct that affects the overall life satisfaction, emotional well-being, and functioning of individuals. The aim of our study was to assess the quality of life of dental students at one U.S. dental school, using the World Health Organization Quality of Life (WHOQOL)-BREF, a multi-dimensional, cross-cultural, validated, and reliable survey instrument. Of the 1,437 students invited to participate, 401 students responded, but 17 were excluded because of missing data. The final sample consisted of 384 students for an overall response rate of 27%: response rates by year were first year 32.6%, second year 16.9%, third year 26.6%, and fourth year 24.0%. The results showed that the responding students rated their overall quality of life as good. The Physical Health domain had the highest mean score, while the Psychological domain had the lowest. Females reported higher quality of life than males in the Social Relationships domain. Single students were found to have a lower perceived quality of life than married students. Older students were found to have lower perceived quality of life in the Physical Health and Environment domains. Physical Health domain scores were significantly higher for fourth-year than first-year respondents, while Psychological domain scores were significantly lower for third-year than first-year respondents. Further research is needed to explore the effect of dental school on the quality of life of dental students. Targeted programs to impact students' quality of life at various points in the curriculum may be beneficial.

Concepts: Public health, Human, Response rate, Life, Education, Quality, Personal life, World Health Organization


Response rates to health-related surveys are declining. This study tested two strategies to improve the response rate to a health psychology survey mailed through English general practices: (1) sending a shortened questionnaire and (2) offering a monetary incentive to return a completed questionnaire.

Concepts: Response rate, Clinical psychology, Applied psychology


Anonymous survey methods appear to promote greater disclosure of sensitive or stigmatizing information compared to non-anonymous methods. Higher disclosure rates have traditionally been interpreted as being more accurate than lower rates. We examined the impact of 3 increasingly private mailed survey conditions–ranging from potentially identifiable to completely anonymous, on survey response and on respondents' representativeness of the underlying sampling frame–completeness in answering sensitive survey items, and disclosure of sensitive information. We also examined the impact of 2 incentives ($10 versus $20) on these outcomes.

Concepts: Sampling, Response rate, Randomized controlled trial, Rates, Information, Reaction rate, Statistical survey, Community Charge


Background Mantle-cell lymphoma is generally incurable. Despite high rates of complete response after initial immunochemotherapy followed by autologous stem-cell transplantation, patients have relapses. We investigated whether rituximab maintenance therapy at a dose of 375 mg per square meter of body-surface area administered every 2 months for 3 years after transplantation would prolong the duration of response. Methods In a phase 3 trial involving 299 patients who were younger than 66 years of age at diagnosis, we randomly assigned 240 patients to receive rituximab maintenance therapy or to undergo observation after autologous stem-cell transplantation (120 patients per group); 59 patients did not undergo randomization. The primary end point was event-free survival (with an event defined as disease progression, relapse, death, allergy to rituximab, or severe infection) after transplantation among patients who underwent randomization. Results After four courses of immunochemotherapy induction (rituximab, dexamethasone, cytarabine, and a platinum derivative [R-DHAP]), the overall response rate was 89%, and the complete response rate 77%. Transplantation was performed in 257 patients. The median follow-up from randomization after transplantation was 50.2 months (range, 46.4 to 54.2). Starting from randomization, the rate of event-free survival at 4 years was 79% (95% confidence interval [CI], 70 to 86) in the rituximab group versus 61% (95% CI, 51 to 70) in the observation group (P=0.001). The rate of progression-free survival at 4 years was 83% (95% CI, 73 to 88) in the rituximab group versus 64% (95% CI, 55 to 73) in the observation group (P<0.001). The rate of overall survival was 89% (95% CI, 81 to 94) in the rituximab group versus 80% (95% CI, 72 to 88) in the observation group (P=0.04). According to a Cox regression unadjusted analysis, the rate of overall survival at 4 years was higher in the rituximab group than in the observation group (hazard ratio for death, 0.50; 95% CI, 0.26 to 0.99; P=0.04). Conclusions Rituximab maintenance therapy after transplantation prolonged event-free survival, progression-free survival, and overall survival among patients with mantle-cell lymphoma who were younger than 66 years of age at diagnosis. (Funded by Roche and Amgen; LyMa number, NCT00921414 .).

Concepts: Sampling, Proportional hazards models, Response rate, Therapy, Relapse, Randomness, Hazard ratio