Integration of child life into adult oncology: A mixed-methods feasibility study.

BACKGROUND: Cancer in a loved one can have negative effects on child health and development. Child Life Specialists (CLSs) specialize in assisting children understand and cope with difficult medical scenarios but are generally not available in adult care facilities to support the needs of patient-families with minor children. We conducted a mixed-methods study of the implementation of a pilot CLS program at a tertiary oncology centre. METHODS: We collected administrative and clinical data on referred families; encounter data; and patient-reported questionnaire data before and 2 months after engagement with the program. RESULTS: Over the initial 10 months, 98 families were referred, 91 of whom engaged through a total of 257 clinical encounters. The cancer patient in the family was most commonly a woman with a mean age of 45 years and in the role of mother. Breast cancer was the most common diagnosis (24%) and 78% of patients had stage IV disease. Most families had >1 child at home, and children were most commonly school-aged (5-14y). Phone and Hospital/Clinic visits accounted for the largest portion of CLS time. Interventions ranged from diagnosis education through to bereavement support. Most cancer patients indicated that the program was helpful to them and their families. There were trends of moderate improvements on patient reported outcomes. CONCLUSION: Our study was able to provide an understanding of the initial CLS program operations to guide program development and future study. Such a program holds promise as an important aspect of adult oncology family-centered care.

Early-stage Hodgkin lymphoma in the modern era: simulation modelling to delineate long-term patient outcomes.

We developed a novel simulation model integrating multiple data sets to project long-term outcomes with contemporary therapy for early-stage Hodgkin lymphoma (ESHL), namely combined modality therapy (CMT) versus chemotherapy alone (CA) via 18 F-fluorodeoxyglucose positron emission tomography response-adaption. The model incorporated 3-year progression-free survival (PFS), probability of cure with/without relapse, frequency of severe late effects (LEs), and 35-year probability of LEs. Furthermore, we generated estimates for quality-adjusted life years (QALYs) and unadjusted survival (life years, LY) and used model projections to compare outcomes for CMTversusCA for two index patients. Patient 1: a 25-year-old male with favourable ESHL (stage IA); Patient 2: a 25-year-old female with unfavourable ESHL (stage IIB). Sensitivity analyses assessed the impact of alternative assumptions for LE probabilities. For Patient 1, CMT was superior to CA (CMT incremental gain = 0·11 QALYs, 0·21 LYs). For Patient 2, CA was superior to CMT (CA incremental gain = 0·37 QALYs, 0·92 LYs). For Patient 1, the advantage of CMT changed minimally when the proportion of severe LEs was reduced from 20% to 5% (0·15 QALYs, 0·43 LYs), whereas increasing the severity proportion for Patient 2's LEs from 20% to 80% enhanced the advantage of CA (1·1 QALYs, 6·5 LYs). Collectively, this detailed simulation model quantified the long-term impact that varied host factors and alternative contemporary treatments have in ESHL.

Minimal clinically important differences in the EORTC QLQ-C30 and brief pain inventory in patients undergoing re-irradiation for painful bone metastases.

PURPOSE: The EORTC QLQ-C30 and the Brief Pain Inventory (BPI) are validated tools for measuring quality of life (QOL) and the impact of pain in patients with advanced cancer. Interpretation of these instrument scores can be challenging and it is difficult to know what numerical changes translate to clinically significant impact in patients' lives. To address this issue, our study sought to establish the minimal clinically important differences (MCID) for these two instruments in a prospective cohort of patients with advanced cancer and painful bone metastases. METHODS: Both anchor-based and distribution-based methods were used to estimate the MCID scores from patients enrolled in a randomized phase III trial evaluating two different re-irradiation treatment schedules. For the anchor-based method, the global QOL item from the QLQ-C30 was chosen as the anchor. Spearman correlation coefficients were calculated for all items and only those items with moderate or better correlation (|r| ≥ 0.30) with the anchor were used for subsequent analysis. A 10-point difference in the global QOL score was used to classify improvement and deterioration, and the MCID scores were calculated for each of these categories. These results were compared with scores obtained by the distribution-method, which estimates the MCID purely from the statistical characteristics of the sample population. RESULTS: A total of 375 patients were included in this study with documented pain responses and completed QOL questionnaires at 2 months. 9/14 items in the QLQ-C30 and 6/10 items in the BPI were found to have moderate or better correlation with the anchor. For deterioration, statistically significant MCID scores were found in all items of the QLQ-C30 and BPI. For improvement, statistically significant MCID scores were found in 7/9 items of the QLQ-C30 and 2/6 items of the BPI. The MCID scores for deterioration were uniformly higher than the MCIDs for improvement. Using the distribution-based method, there was good agreement between the 0.5 standard deviation (SD) values and anchor-based scores for deterioration. For improvement, there was less agreement and the anchor-based scores were lower than the 0.5 SD values obtained from the distribution-based method. CONCLUSION: We present MCID scores for the QLQ-C30 and BPI instruments obtained from a large cohort of patients with advanced cancer undergoing re-irradiation for painful bone metastases. The results from this study were compared to other similar studies which showed larger MCID scores for improvement compared to deterioration. We hypothesize that disease trajectory and patient expectations are important factors in understanding the contrasting results. The results of this study can guide clinicians and researchers in the interpretation of these instruments.

Salvage chemotherapy and autologous stem cell transplantation for transformed indolent lymphoma: a subset analysis of NCIC CTG LY12.

The treatment of transformed indolent lymphoma (TRIL) often includes salvage chemotherapy (SC) and autologous stem cell transplant (ASCT). NCIC CTG LY12 is a randomized phase 3 trial comparing gemcitabine, dexamethasone, and cisplatin (GDP) with dexamethasone, cytarabine, and cisplatin (DHAP) before ASCT. This analysis compares the results of SC and ASCT for TRIL with de novo diffuse large B-cell lymphoma (DLBCL). Six-hundred nineteen patients with relapsed/refractory aggressive non-Hodgkin lymphoma were randomized to GDP or DHAP; 87 patients (14%) had TRIL and 429 (69%) had DLBCL. The response rate to SC was 47% in TRIL and 45% in DL (P = .81). Transplantation rates were similar: TRIL 53% and DL 52% (P = 1.0). With a median follow-up of 53 months, 4 year overall survival was 39% for TRIL and 41% for DL (P = .78); 4 year event-free survival (EFS) was 27% for TRIL and 27% for DL (P = .83). Post-ASCT, 4-year EFS was 45% for TRIL and 46% for DL. Histology (TRIL or DL) was not a predictor of any outcome in multivariate models. Patients with relapsed or refractory TRIL and DLBCL have similar outcomes with SC and ASCT; this therapy should be considered the standard of care for patients with TRIL who have received prior systemic chemotherapy. NCIC CTG LY12 is registered at ClinicalTrials.gov as #NCT00078949.

Classification of painful bone metastases as mild, moderate, or severe using both EORTC QLQ-C15-PAL and EORTC QLQ-BM22.

PURPOSE: Previous studies have determined optimal cut points (CPs) for the classification of pain severity as mild, moderate, or severe using only the Brief Pain Inventory (BPI) or the BPI in conjunction with a quality of life (QOL) tool. The purpose of our study was to determine the optimal CPs based on correlation with only QOL outcomes. METHODS: We conducted an analysis of 298 patients treated with radiation therapy for painful bone metastases on a phase III randomized trial. Prior to treatment, patients provided their worst pain score on a scale of 0 (no pain) to 10 (worst possible pain), as well as completed the European Organization of Cancer Research and Treatment (EORTC) QOL Questionnaire Bone Metastases module (QLQ-BM22) and the EORTC QOL Questionnaire Core-15 Palliative (QLQ-C15-PAL). Optimal CPs were determined to be those that yielded the largest F ratio for the between category effect on each subscale of the QLQ-BM22 and QLQ-C15-PAL using the multivariate analysis of variance (MANOVA). RESULTS: The two largest F ratios for Wilk's λ, Pillai's Trace, and Hotelling's Trace were for CPs 5,6 and 5,7. Combining both, the optimal CPs to differentiate between mild, moderate, and severe pain were 5 and 7. Pain scores of 1-5, 6, and 7-10 were classified as mild, moderate, and severe, respectively. Patients with severe pain experienced greater functional interference and poorer QOL when compared to those with mild pain. CONCLUSION: Our results suggest that, based on the impact of pain on QOL measures, pain scores should be classified as follows: 1-5 as mild pain, 6 as moderate pain, and 7-10 as severe pain. Optimal CPs vary depending on the type of outcome measurement used.

Revisiting classification of pain from bone metastases as mild, moderate, or severe based on correlation with function and quality of life.

PURPOSE: The objective of our study was to determine the optimal cut points for classification of pain scores as mild, moderate, and severe based on interference with function and quality of life (QOL). METHODS: We evaluated 822 patients who completed the Brief Pain Inventory (BPI) and/or the European Organization for Research and Treatment of Cancer (EORTC) QOL Questionnaire Core 30 (QLQ-C30) prior to receiving repeat radiation therapy for previously irradiated painful bone metastases. Optimal cut points for mild, moderate, and severe pain were determined by the MANOVA that yielded the largest F ratio for the between category effect on the seven interference items of BPI and the six functional domains of QOL (physical, role, emotional, cognitive, social functioning, and global QOL) as indicated by Pillai's Trace, Wilk's λ, and Hostelling's Trace F statistics. RESULTS: For BPI and for QOL domains separately, the two largest F ratios for Wilk's λ, Pillai's Trace, and Hotelling's Trace F statistics were from the cut points 4, 8 and 6, 8. When combining both, the optimal cut points were 4, 8 with 1-4 (mild), 5-8 (moderate), and 9-10 (severe). With this classification, the mean scores of all the seven interference items in BPI and the six functional domains were all highly statistically different. Patients with severe pain survived significantly shorter than those with mild and moderate pain (p < 0.0001). CONCLUSION: Our analysis supports the classification of pain scores as follows: 1-4 as mild pain, 5-8 as moderate pain, and 9-10 as severe pain. This may facilitate conduct of future clinical trials.

Minimal clinically important differences in the EORTC QLQ-BM22 and EORTC QLQ-C15-PAL modules in patients with bone metastases undergoing palliative radiotherapy.

PURPOSE: Validated tools for evaluating quality of life (QOL) in patients with bone metastases include the EORTC QLQ-BM22 and QLQ-C15-PAL modules. A statistically significant difference in metric scores may not be clinically significant. To aid in their interpretation, we performed analyses to determine the minimal clinically important differences (MCID) for these QOL instruments. METHODS: Both anchor-based and distribution-based methods were used to determine the MCID among patients with bone metastases enrolled in a randomized phase III trial. For the anchor-based approach, overall QOL as measured by the QLQ-C15-PAL module was used as the anchor and only the subscales with moderate or better correlation were used for subsequent MCID analysis. In the anchor-based approach, patients were classified as improved, stable or deteriorated by the change in the overall QOL score from baseline to follow-up after 42 days. The MCID and confidence interval was then calculated for all subscales. In the distribution-based approach, the MCID was expressed as a proportion of the standard deviation and standard error measurement from the subscale score distribution. RESULTS: A total of 204 patients completed the questionnaires at baseline and follow-up. Only the dyspnea and insomnia subscales did not have at least moderate correlation with the overall QOL anchor. Using the anchor-based approach, 10/11 subscales had an MCID score significantly different than 0 for improvement and 3/11 subscales had a significant MCID score for deterioration. The magnitude of MCID scores was higher for improvement in comparison with deterioration. For improvement, the anchor-based approach showed good agreement with the distribution-based approach when using 0.5 SD as the MCID. However, there was greater lack of agreement between these approaches for deterioration. CONCLUSION: We present the MCID scores for the EORTC QLQ-BM22 and QLQ-C15-PAL QOL instruments. The results of this study can guide clinicians in the interpretation of these instruments. CLINICAL TRIALS REGISTRY: NCT01248585.

Dexamethasone in the prophylaxis of radiation-induced pain flare after palliative radiotherapy for bone metastases: a double-blind, randomised placebo-controlled, phase 3 trial.

BACKGROUND: Pain flare occurs after palliative radiotherapy, and dexamethasone has shown potential for prevention of such flare. We aimed to compare the efficacy of dexamethasone with that of placebo in terms of reduction of incidence of pain flare. METHODS: In this double-blind, randomised, placebo-controlled phase 3 trial, patients from 23 Canadian centres were randomly allocated (1:1) with a web-based system and minimisation algorithm to receive either two 4 mg dexamethasone tablets or two placebo tablets taken orally at least 1 h before the start of radiation treatment (a single 8 Gy dose to bone metastases; day 0) and then every day for 4 days after radiotherapy (days 1-4). Patients were eligible if they had a non-haematological malignancy and bone metastasis (or metastases) corresponding to the clinically painful area or areas. Patients reported their worst pain scores and opioid analgesic intake before treatment and daily for 10 days after radiation treatment. They completed the European Organisation for Research and Treatment of Cancer (EORTC) quality of life QLQ-C15-PAL, the bone metastases module (EORTC QLQ-BM22), and the Dexamethasone Symptom Questionnaire at baseline, and at days 10 and 42 after radiation treatment. Pain flare was defined as at least a two-point increase on a scale of 0-10 in the worst pain score with no decrease in analgesic intake, or a 25% or greater increase in analgesic intake with no decrease in the worst pain score from days 0-10, followed by a return to baseline levels or below. Primary analysis of incidence of pain flare was by intention-to-treat (patients with missing primary data were classified as having pain flare). This study is registered with ClinicalTrials.gov, number NCT01248585, and is completed. FINDINGS: Between May 30, 2011, and Dec 11, 2014, 298 patients were enrolled. 39 (26%) of 148 patients randomly allocated to the dexamethasone group and 53 (35%) of 150 patients in the placebo group had a pain flare (difference 8·9%, lower 95% confidence bound 0·0, one-sided p=0·05). Two grade 3 and one grade 4 biochemical hyperglycaemic events occurred in the dexamethasone group (without known clinical effects) compared with none in the placebo group. The most common adverse events were bone pain (61 [41%] of 147 vs 68 [48%] of 143), fatigue (58 [39%] of 147 vs 49 [34%] of 143), constipation (47 [32%] of 147 vs 37 [26%] of 143), and nausea (34 [23%] of 147 vs 34 [24%] of 143), most of which were mild grade 1 or 2. INTERPRETATION: Dexamethasone reduces radiation-induced pain flare in the treatment of painful bone metastases. FUNDING: The NCIC CTG's programmatic grant from the Canadian Cancer Society Research Institute.

Thalidomide-prednisone maintenance following autologous stem cell transplant for multiple myeloma: effect on thrombin generation and procoagulant markers in NCIC CTG MY.10.

Venous thromboembolism (VTE) has an increased incidence in patients with multiple myeloma (MM), especially during chemotherapy. Mechanisms including upregulation of procoagulant factors, such as factor VIII, have been postulated. The National Cancer Institute of Canada Clinical Trials Group MY.10 phase III clinical trial compared thalidomide-prednisone to observation for 332 patients with MM post-autologous stem cell transplantation (ASCT), with a primary endpoint of overall survival and various secondary endpoints including the incidence of VTE. One hundred and fifty-three patients had biomarker data, including D-dimer, factor VIII and thrombin anti-thrombin (TAT) levels collected post-ASCT at baseline and 2 months after intervention investigating in-vivo thrombin generation. Differences between the time-points included a significant reduction over time in D-dimer, factor VIII and TAT levels in the observation group and sustained elevation of D-dimer, significant increase in factor VIII and reduction in TAT levels in the thalidomide-prednisone group. Eight VTE events were reported in this subset of study patients, all in the thalidomide-prednisone arm, with a trend to increase in D-dimer levels over time in those patients with VTE. This study provides physiological and clinical evidence for an increased risk of VTE associated with thalidomide-prednisone maintenance therapy post-ASCT for MM.

ABVD alone versus radiation-based therapy in limited-stage Hodgkin's lymphoma.

BACKGROUND: Chemotherapy plus radiation treatment is effective in controlling stage IA or IIA nonbulky Hodgkin's lymphoma in 90% of patients but is associated with late treatment-related deaths. Chemotherapy alone may improve survival because it is associated with fewer late deaths. METHODS: We randomly assigned 405 patients with previously untreated stage IA or IIA nonbulky Hodgkin's lymphoma to treatment with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) alone or to treatment with subtotal nodal radiation therapy, with or without ABVD therapy. Patients in the ABVD-only group, both those with a favorable risk profile and those with an unfavorable risk profile, received four to six cycles of ABVD. Among those assigned to subtotal nodal radiation therapy, patients who had a favorable risk profile received subtotal nodal radiation therapy alone and patients with an unfavorable risk profile received two cycles of ABVD plus subtotal nodal radiation therapy. The primary end point was 12-year overall survival. RESULTS: The median length of follow-up was 11.3 years. At 12 years, the rate of overall survival was 94% among those receiving ABVD alone, as compared with 87% among those receiving subtotal nodal radiation therapy (hazard ratio for death with ABVD alone, 0.50; 95% confidence interval [CI], 0.25 to 0.99; P=0.04); the rates of freedom from disease progression were 87% and 92% in the two groups, respectively (hazard ratio for disease progression, 1.91; 95% CI, 0.99 to 3.69; P=0.05); and the rates of event-free survival were 85% and 80%, respectively (hazard ratio for event, 0.88; 95% CI, 0.54 to 1.43; P=0.60). Among the patients randomly assigned to ABVD alone, 6 patients died from Hodgkin's lymphoma or an early treatment complication and 6 died from another cause; among those receiving radiation therapy, 4 deaths were related to Hodgkin's lymphoma or early toxic effects from the treatment and 20 were related to another cause. CONCLUSIONS: Among patients with Hodgkin's lymphoma, ABVD therapy alone, as compared with treatment that included subtotal nodal radiation therapy, was associated with a higher rate of overall survival owing to a lower rate of death from other causes. (Funded by the Canadian Cancer Society and the National Cancer Institute; HD.6 ClinicalTrials.gov number, NCT00002561.).

EBV DNA: a Hodgkin lymphoma biomarker?

In this issue of Blood, Kanakry and colleagues report that increased pretreatment levels of plasma Epstein Barr virus DNA (EBV-DNA), as determined by quantitative real-time polymerase chain reaction (QRT-PCR), are associated with inferior outcomes among patients with previously untreated, advanced-stage Hodgkin lymphoma.

A randomized phase 3 trial of thalidomide and prednisone as maintenance therapy after ASCT in patients with MM with a quality-of-life assessment: the National Cancer Institute of Canada Clinicals Trials Group Myeloma 10 Trial.

We conducted a randomized, controlled trial comparing thalidomide-prednisone as maintenance therapy with observation in 332 patients who had undergone autologous stem cell transplantation with melphalan 200 mg/m2. The primary end point was overall survival (OS); secondary end points were myeloma-specific progression-free survival,progression-free survival, incidence of venous thromboembolism, and health-related quality of life (HRQoL). With a median follow-up of 4.1 years, no differences in OS between thalidomide-prednisone and observation were detected (respective 4-year estimates of 68% vs 60%, respectively; hazard ratio = 0.77; P = .18); thalidomide-prednisone was associated with superior myeloma-specific progression-free survival and progression-free survival (for both outcomes, the 4-year estimates were 32% vs 14%; hazard ratio = 0.56; P < .0001) and more frequent venous thromboembolism (7.3% vs none; P = .0004). Median survival after first disease recurrence was 27.7 months with thalidomide-prednisone and 34.1 months in the observation group. Nine second malignancies were observed with thalidomide-prednisone versus 6 in the observation group. Those allocated to thalidomide-prednisone reported worse HRQoL with respect to cognitive function, dyspnea, constipation, thirst, leg swelling, numbness, dry mouth, and balance problems. We conclude that maintenance therapy with thalidomide-prednisone after autologous stem cell transplantation improves the duration of disease control, but is associated with worsening of patient-reported HRQoL and no detectable OS benefit.

Integrating health-related quality of life findings from randomized clinical trials into practice: an international study of oncologists' perspectives.

PURPOSE: Although health-related quality of life (HRQL) is increasingly assessed in randomized controlled trials (RCTs), HRQL findings are not always incorporated into clinical decision making. We examined the current perspectives of oncologists on the use of HRQL findings from RCTs, and variation of these perspectives between countries and specialties. METHODS: A cross-sectional e-survey of oncologist members of the NCIC Clinical Trials Group, the United Kingdom National Cancer Research Institute Clinical Studies Groups, and the Australia/New Zealand cancer clinical trials network was conducted. Respondents reported their perceptions of the usefulness of RCT HRQL outcomes for informing practice, their use of HRQL findings in practice, barriers/facilitators to this use, and preferences for HRQL data presentation in RCT publications. Chi-square tests compared responses between countries and specialties. RESULTS: A total of 396 oncologists participated (estimated response rate: 30%). The most frequently reported specialties were medical (46%) and radiation (37%) oncology. HRQL findings from RCTs were reported as useful (73%), but were infrequently used to guide clinical decisions with patients. Perceived barriers were lack of time (67%) and understanding (57%), and concerns about generalizability of results (68%). Identified facilitators included joint publication of HRQL/clinical outcomes (96%) and summary of clinical implications of HRQL findings in RCT publications (76%). Use of HRQL findings, perceived barriers/facilitators, and presentation preferences did not differ by country or specialty. CONCLUSIONS: Oncologists support HRQL findings from RCTs, but perceive important barriers to their use in clinical decision making, regardless of country or specialty. Combined, clear reporting of HRQL/clinical data may facilitate their clinical application.

Single versus multiple fractions of repeat radiation for painful bone metastases: a randomised, controlled, non-inferiority trial.

BACKGROUND: Although repeat radiation treatment has been shown to palliate pain in patients with bone metastases from multiple primary origin sites, data for the best possible dose fractionation schedules are lacking. We aimed to assess two dose fractionation schedules in patients with painful bone metastases needing repeat radiation therapy. METHODS: We did a multicentre, non-blinded, randomised, controlled trial in nine countries worldwide. We enrolled patients 18 years or older who had radiologically confirmed, painful (ie, pain measured as ≥2 points using the Brief Pain Inventory) bone metastases, had received previous radiation therapy, and were taking a stable dose and schedule of pain-relieving drugs (if prescribed). Patients were randomly assigned (1:1) to receive either 8 Gy in a single fraction or 20 Gy in multiple fractions by a central computer-generated allocation sequence using dynamic minimisation to conceal assignment, stratified by previous radiation fraction schedule, response to initial radiation, and treatment centre. Patients, caregivers, and investigators were not masked to treatment allocation. The primary endpoint was overall pain response at 2 months, which was defined as the sum of complete and partial pain responses to treatment, assessed using both Brief Pain Inventory scores and changes in analgesic consumption. Analysis was done by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00080912. FINDINGS: Between Jan 7, 2004, and May 24, 2012, we randomly assigned 425 patients to each treatment group. 19 (4%) patients in the 8 Gy group and 12 (3%) in the 20 Gy group were found to be ineligible after randomisation, and 140 (33%) and 132 (31%) patients, respectively, were not assessable at 2 months and were counted as missing data in the intention-to-treat analysis. In the intention-to-treat population, 118 (28%) patients allocated to 8 Gy treatment and 135 (32%) allocated to 20 Gy treatment had an overall pain response to treatment (p=0·21; response difference of 4·00% [upper limit of the 95% CI 9·2, less than the prespecified non-inferiority margin of 10%]). In the per-protocol population, 116 (45%) of 258 patients and 134 (51%) of 263 patients, respectively, had an overall pain response to treatment (p=0·17; response difference 6·00% [upper limit of the 95% CI 13·2, greater than the prespecified non-inferiority margin of 10%]). The most frequently reported acute radiation-related toxicities at 14 days were lack of appetite (201 [56%] of 358 assessable patients who received 8 Gy vs 229 [66%] of 349 assessable patients who received 20 Gy; p=0·011) and diarrhoea (81 [23%] of 357 vs 108 [31%] of 349; p=0·018). Pathological fractures occurred in 30 (7%) of 425 patients assigned to 8 Gy and 20 (5%) of 425 assigned to 20 Gy (odds ratio [OR] 1·54, 95% CI 0·85-2·75; p=0·15), and spinal cord or cauda equina compressions were reported in seven (2%) of 425 versus two (<1%) of 425, respectively (OR 3·54, 95% CI 0·73-17·15; p=0·094). INTERPRETATION: In patients with painful bone metastases requiring repeat radiation therapy, treatment with 8 Gy in a single fraction seems to be non-inferior and less toxic than 20 Gy in multiple fractions; however, as findings were not robust in a per-protocol analysis, trade-offs between efficacy and toxicity might exist. FUNDING: Canadian Cancer Society Research Institute, US National Cancer Institute, Cancer Council Australia, Royal Adelaide Hospital, Dutch Cancer Society, and Assistance Publique-Hôpitaux de Paris.

Point/counterpoint: early-stage Hodgkin lymphoma and the role of radiation therapy.

The results of recent clinical trials for the management of limited-stage Hodgkin lymphoma have led to considerable debate, especially regarding the role of radiation therapy. This review highlights those recent trials and provides perspectives regarding their interpretation from a radiation oncologist and a hematologist. The trial protocol is available at http://www.nejm.org/doi/suppl/10.1056/NEJMoa1111961/suppl_file/nejmoa1111961_protocol.pdf.

A pilot randomized trial of adjuvant rituximab or placebo for nonsplenectomized patients with immune thrombocytopenia.

The benefit of adding rituximab to standard treatment in nonsplenectomized patients with primary immune thrombocytopenia (ITP) is uncertain. We performed a pilot randomized trial to determine the feasibility of recruitment, protocol adherence, and blinding of a larger trial of rituximab versus placebo; and to evaluate the potential efficacy of adjuvant rituximab in ITP. Nonsplenectomized adults with newly diagnosed or relapsed ITP who were receiving standard ITP therapy for a platelet count below 30 × 10(9)/L were randomly allocated to receive 4 weekly infusions of 375 mg/m(2) rituximab or saline placebo. Sixty patients were recruited over 46 months, which was slower than anticipated. Protocol adherence and follow-up targets were achieved, and blinding was successful for research staff but not for patients. After 6 months, there was no difference between rituximab and placebo groups for the composite outcome of any platelet count below 50 × 10(9)/L, significant bleeding or rescue treatment once standard treatment was stopped (21/32 [65.6%] vs 21/26 [80.8%]; relative risk = 0.81, 95% confidence intervals, 0.59%-1.11%). Timely accrual poses a challenge to the conduct of a large randomized trial of rituximab for presplenectomy ITP. No difference in the frequency of the composite outcome was observed in this pilot trial (registered at www.clinicaltrials.gov NCT00372892).

Patient and Provider Attitudes and Preferences Regarding Early Palliative Care Delivery for Patients with Advanced Gastrointestinal Cancers: A Prospective Survey.

Early integrated palliative care (EIPC) for patients with advanced cancers requires the involvement of family doctors (FDs) and oncologists. We compared attitudes between patients and their providers regarding the delivery of EIPC. Patients with newly diagnosed incurable gastrointestinal (GI) cancer at a tertiary cancer centre in Ontario, Canada, were surveyed using a study-specific instrument regarding the importance of and preferences for accessing support across eight domains of palliative care. Physicians within the circle of care completed a parallel survey for each patient. The concordance between patient and physician responses was analyzed. A total of 66 patients were surveyed (median age 69, 35% female). All had an oncologist, 12% had a specialist palliative care provider (SPC), and 97% had an FD, but only 41% listed the FD as part of the care team. In total, 95 providers responded (oncologist = 68, FD = 21, SPC = 6; response rate 92%; 1-3 physician responses per patient). Disease management and physical concerns were most important to patients. Patients preferred to access care in these domains from oncologists or SPCs. For all other domains, most patients attributed primary responsibility to self or family rather than any healthcare provider. Thus, concordance was poor between patient and physician responses. Across most domains of palliative care, we found low agreement between cancer patients and their physicians regarding responsibilities for care, with FDs appearing to have limited involvement at this stage.

Development and testing of a lymphoma clinical trial-specific frailty index: a secondary analysis of the NCIC-CTG LY.12 clinical trial.

The prevalence of frailty in clinical trials of lymphoma is unknown. We conducted a secondary analysis of the phase III LY.12 trial in which patients with relapsed aggressive non-Hodgkin lymphoma were randomized to different salvage regimens before autologous stem cell transplant. The primary objective was to construct a lymphoma clinical trials-specific frailty index (LyFI) using previously described methods. The secondary objective was to describe the association of frailty withover all and event-free survival (OS, EFS). The LyFI was constructed using 619 patients, and11% (N = 70) were classified as frail. Frailty was associated with EFS (HR 1.94, 95%CI 1.53-2.46) and OS (HR 2.01, 95%CI 1.57-2.58) in univariable analysis, but was only significant as a continuous (not binary) variable in multivariable analysis controlling for prognostic score, suggesting limitations of a FI in this trial population. Future work could validate the FI using clinical assessments and/or apply it to an older trial population.

A population-based study of cardiac morbidity among Hodgkin lymphoma patients with preexisting heart disease.

The risk of cardiac hospitalization (CH) in Hodgkin lymphoma (HL) patients with preexisting heart disease was evaluated. Patients with HL were identified from a population-based registry (N = 3964). Data were abstracted from records of a randomly selected subcohort (N = 1096). A population-based registry was used to identify CH. Factors associated with CH and the incidence of CH after HL were estimated with competing risk models. Preexisting heart disease was the strongest predictor of posttreatment CH (hazard ratio = 3.98, P < .001) and significantly modified (P = .01) the effect of treatment on the risk of CH. Among patients with preexisting heart disease, treatment with mediastinal radiation therapy plus doxorubicin-based chemotherapy was associated with a 10-year incidence of CH more than 20% higher than treatment with chemotherapy alone. There is a high risk of CH after mediastinal radiation therapy plus doxorubicin-based chemotherapy among patients with preexisting heart disease; this is an important consideration when weighing treatment options, and in the follow-up of these patients.