A quality of life subscale for terminally ill cancer patients

A subscale was developed to assess the quality of life of cancer patients with a life expectancy of six months or less. Phase I of this study identified the major concerns of 74 terminally ill cancer patients (19 with breast cancer, 19 with lung cancer, 18 with colorectal cancer, 9 with renal cell cancer, 9 with prostate cancer), 39 family caregivers, and 20 health care professionals. Patients interviewed were being treated at the University of Texas M. D. Anderson Cancer Center or at the Hospice at the Texas Medical Center in Houston. In Phase II, 120 patients (30 with breast cancer, 30 with lung cancer, 30 with colorectal cancer, 15 with prostate cancer, and 15 with renal cell cancer) rated the importance of these concerns for quality of life. Items retained for the subscale were rated as "extremely important" or "very important" by at least 60% of the sample and were reported as being applicable by at least two-thirds of the sample. The 61 concerns that were identified were formatted as a questionnaire for Phase III. In Phase III, 356 patients (89 with breast cancer, 88 with lung cancer, 88 with colorectal cancer, 44 with prostate cancer, and 47 with renal cell cancer) were interviewed to determine the subscale's reliability and sensitivity to change in clinical status. Both factor analysis and item response theory supported the inclusion of the same 35 items for the subscale. Internal consistency reliability was moderate to high for the subscale's domains: spiritual (0.87), existential (0.76), medical care (0.68), symptoms (0.67), social/family (0.66), and emotional (0.61). Test-retest correlation coefficients also were high for the domains: social/family (0.86), emotional (0.83), medical care (0.83), spiritual (0.75), existential (0.75), and symptoms (0.81).^ In addition, concurrent validity was supported by the high correlation between the subscale's symptom domain and symptom items from the European Organization for Research and Treatment of Cancer (EORTC) scale (r = 0.74). Patients' functional status was assessed with the Eastern Cooperative Oncology Group (ECOG) Performance status rating. When ECOG categories were compared to subscale domains, patients who scored lower in functional status had lower scores in the spiritual, existential, social/family, and emotional domains. Patients who scored lower in physical well-being had higher scores in the symptom domain. Patient scores in the medical care domain were similar for each ECOG category. The results of this study support the subscale's use in assessing quality of life and the outcomes of palliative treatment for cancer patients in their last six months of life. ^

Design and implementation of a multicriteria medical decision support system for diagnosis and treatment

Health care providers face the problem of trying to make decisions with inadequate information and also with an overload of (often contradictory) information. Physicians often choose treatment long before they know which disease is present. Indeed, uncertainty is intrinsic to the practice of medicine. Decision analysis can help physicians structure and work through a medical decision problem, and can provide reassurance that decisions are rational and consistent with the beliefs and preferences of other physicians and patients. ^ The primary purpose of this research project is to develop the theory, methods, techniques and tools necessary for designing and implementing a system to support solving medical decision problems. A case study involving “abdominal pain” serves as a prototype for implementing the system. The research, however, focuses on a generic class of problems and aims at covering theoretical as well as practical aspects of the system developed. ^ The main contributions of this research are: (1) bridging the gap between the statistical approach and the knowledge-based (expert) approach to medical decision making; (2) linking a collection of methods, techniques and tools together to allow for the design of a medical decision support system, based on a framework that involves the Analytic Network Process (ANP), the generalization of the Analytic Hierarchy Process (AHP) to dependence and feedback, for problems involving diagnosis and treatment; (3) enhancing the representation and manipulation of uncertainty in the ANP framework by incorporating group consensus weights; and (4) developing a computer program to assist in the implementation of the system. ^

Trastuzumab treatment beyond progression in advanced breast cancer: patterns of care in six Swiss breast cancer centers.

BACKGROUND Trastuzumab is an established treatment for HER2-positive breast cancer (BC). We analyzed Swiss patterns of care in patients with HER2-positive BC after disease progression on trastuzumab-containing therapy for metastatic BC (MBC). PATIENTS AND METHODS A retrospective analysis was performed in six Swiss BC centers. Patients with HER2-positive MBC treated with at least one infusion of trastuzumab for advanced disease between January 2006 and December 2007 were identified. Treatment patterns in first and further lines were analyzed. RESULTS All of the 72 identified patients received trastuzumab as their first palliative anti-HER2 therapy, either as monotherapy (n = 23) or in combination with chemotherapy (typically taxane or vinorelbine; n = 49). Median time to progression was 8.1, 8.0 and 7.9 months in the monotherapy, trastuzumab-taxane and trastuzumab-vinorelbine cohorts, respectively. After progression on first-line anti-HER2 therapy, trastuzumab was continued in 67 of 68 patients who received further therapy. One patient received second-line lapatinib plus capecitabine. The median duration of anti-HER2 therapy was 20 months. Patients received a median of 4 lines of anti-HER2 therapy. CONCLUSIONS Durable responses were achieved with repeated exposure to anti-HER2 therapy. In a selected patient population, trastuzumab monotherapy appears to be a reasonable first-line treatment option.

Higher emotional distress in female partners of cancer patients: prevalence and patient-partner interdependencies in a 3-year cohort

OBJECTIVE: Assessment and treatment of psychological distress in cancer patients was recognized as a major challenge. The role of spouses, caregivers, and significant others became of salient importance not only because of their supportive functions but also in respect to their own burden. The purpose of this study was to assess the amount of distress in a mixed sample of cancer patients and their partners and to explore the dyadic interdependence. METHODS: An initial sample of 154 dyads was recruited, and distress questionnaires (Hospital Anxiety and Depression Scale, Symptom Checklist 9-Item Short Version and 12-Item Short Form Health Survey) were assessed over four time points. Linear mixed models and actor-partner interdependence models were applied. RESULTS: A significant proportion of patients and their partners (up to 40%) reported high levels of anxiety, depression, psychological distress, and low quality of life over the course of the investigation. Mixed model analyses revealed that higher risks for clinical relevant anxiety and depression in couples exist for female patients and especially for female partners. Although psychological strain decreased over time, the risk for elevated distress in female partners remained. Modeling patient-partner interdependence over time stratified by patients' gender revealed specific effects: a moderate correlation between distress in patients and partners, and a transmission of distress from male patients to their female partners. CONCLUSIONS: Our findings provide empirical support for gender-specific transmission of distress in dyads coping with cancer. This should be considered as an important starting point for planning systemic psycho-oncological interventions and conceptualizing further research.

Variability in the Treatment of Elderly Patients with Stage IIIA (N2) Non–Small-Cell Lung Cancer

INTRODUCTION: We evaluated treatment patterns of elderly patients with stage IIIA (N2) non-small-cell lung cancer (NSCLC). METHODS: The use of surgery, chemotherapy, and radiation for patients with stage IIIA (T1-T3N2M0) NSCLC in the Surveillance, Epidemiology, and End Results-Medicare database from 2004 to 2007 was analyzed. Treatment variability was assessed using a multivariable logistic regression model that included treatment, patient, tumor, and census track variables. Overall survival was analyzed using the Kaplan-Meier approach and Cox proportional hazard models. RESULTS: The most common treatments for 2958 patients with stage IIIA (N2) NSCLC were radiation with chemotherapy (n = 1065, 36%), no treatment (n = 534, 18%), and radiation alone (n = 383, 13%). Surgery was performed in 709 patients (24%): 235 patients (8%) had surgery alone, 40 patients (1%) had surgery with radiation, 222 patients had surgery with chemotherapy (8%), and 212 patients (7%) had surgery, chemotherapy, and radiation. Younger age (p < 0.0001), lower T-status (p < 0.0001), female sex (p = 0.04), and living in a census track with a higher median income (p = 0.03) predicted surgery use. Older age (p < 0.0001) was the only factor that predicted that patients did not get any therapy. The 3-year overall survival was 21.8 ± 1.5% for all patients, 42.1 ± 3.8% for patients that had surgery, and 15.4 ± 1.5% for patients that did not have surgery. Increasing age, higher T-stage and Charlson Comorbidity Index, and not having surgery, radiation, or chemotherapy were all risk factors for worse survival (all p values < 0.001). CONCLUSIONS: Treatment of elderly patients with stage IIIA (N2) NSCLC is highly variable and varies not only with specific patient and tumor characteristics but also with regional income level.

Trends and outcomes in the use of surgery and radiation for the treatment of locally advanced esophageal cancer: a propensity score adjusted analysis of the surveillance, epidemiology, and end results registry from 1998 to 2008

We examined outcomes and trends in surgery and radiation use for patients with locally advanced esophageal cancer, for whom optimal treatment isn't clear. Trends in surgery and radiation for patients with T1-T3N1M0 squamous cell or adenocarcinoma of the mid or distal esophagus in the Surveillance, Epidemiology, and End Results database from 1998 to 2008 were analyzed using generalized linear models including year as predictor; Surveillance, Epidemiology, and End Results doesn't record chemotherapy data. Local treatment was unimodal if patients had only surgery or radiation and bimodal if they had both. Five-year cancer-specific survival (CSS) and overall survival (OS) were analyzed using propensity-score adjusted Cox proportional-hazard models. Overall 5-year survival for the 3295 patients identified (mean age 65.1 years, standard deviation 11.0) was 18.9% (95% confidence interval: 17.3-20.7). Local treatment was bimodal for 1274 (38.7%) and unimodal for 2021 (61.3%) patients; 1325 (40.2%) had radiation alone and 696 (21.1%) underwent only surgery. The use of bimodal therapy (32.8-42.5%, P = 0.01) and radiation alone (29.3-44.5%, P < 0.001) increased significantly from 1998 to 2008. Bimodal therapy predicted improved CSS (hazard ratios [HR]: 0.68, P < 0.001) and OS (HR: 0.58, P < 0.001) compared with unimodal therapy. For the first 7 months (before survival curve crossing), CSS after radiation therapy alone was similar to surgery alone (HR: 0.86, P = 0.12) while OS was worse for surgery only (HR: 0.70, P = 0.001). However, worse CSS (HR: 1.43, P < 0.001) and OS (HR: 1.46, P < 0.001) after that initial timeframe were found for radiation therapy only. The use of radiation to treat locally advanced mid and distal esophageal cancers increased from 1998 to 2008. Survival was best when both surgery and radiation were used.

Risk of late effects of treatment in children newly diagnosed with standard-risk acute lymphoblastic leukaemia: a report from the Childhood Cancer Survivor Study cohort

BACKGROUND Treatment of patients with paediatric acute lymphoblastic leukaemia has evolved such that the risk of late effects in survivors treated in accordance with contemporary protocols could be different from that noted in those treated decades ago. We aimed to estimate the risk of late effects in children with standard-risk acute lymphoblastic leukaemia treated with contemporary protocols. METHODS We used data from similarly treated members of the Childhood Cancer Survivor Study cohort. The Childhood Cancer Survivor Study is a multicentre, North American study of 5-year survivors of childhood cancer diagnosed between 1970 and 1986. We included cohort members if they were aged 1·0-9·9 years at the time of diagnosis of acute lymphoblastic leukaemia and had received treatment consistent with contemporary standard-risk protocols for acute lymphoblastic leukaemia. We calculated mortality rates and standardised mortality ratios, stratified by sex and survival time, after diagnosis of acute lymphoblastic leukaemia. We calculated standardised incidence ratios and absolute excess risk for subsequent neoplasms with age-specific, sex-specific, and calendar-year-specific rates from the Surveillance, Epidemiology and End Results Program. Outcomes were compared with a sibling cohort and the general US population. FINDINGS We included 556 (13%) of 4329 cohort members treated for acute lymphoblastic leukaemia. Median follow-up of the survivors from 5 years after diagnosis was 18·4 years (range 0·0-33·0). 28 (5%) of 556 participants had died (standardised mortality ratio 3·5, 95% CI 2·3-5·0). 16 (57%) deaths were due to causes other than recurrence of acute lymphoblastic leukaemia. Six (1%) survivors developed a subsequent malignant neoplasm (standardised incidence ratio 2·6, 95% CI 1·0-5·7). 107 participants (95% CI 81-193) in each group would need to be followed-up for 1 year to observe one extra chronic health disorder in the survivor group compared with the sibling group. 415 participants (376-939) in each group would need to be followed-up for 1 year to observe one extra severe, life-threatening, or fatal disorder in the group of survivors. Survivors did not differ from siblings in their educational attainment, rate of marriage, or independent living. INTERPRETATION The prevalence of adverse long-term outcomes in children treated for standard risk acute lymphoblastic leukaemia according to contemporary protocols is low, but regular care from a knowledgeable primary-care practitioner is warranted. FUNDING National Cancer Institute, American Lebanese-Syrian Associated Charities, Swiss Cancer Research.

Predictors of satisfaction with treatment decision, decision-making preferences, and main treatment goals in patients with advanced cancer

Purpose This study investigated satisfaction with treatment decision (SWTD), decision-making preferences (DMP), and main treatment goals, as well as evaluated factors that predict SWTD, in patients receiving palliative cancer treatment at a Swiss oncology network. Patients and methods Patients receiving a new line of palliative treatment completed a questionnaire 4–6 weeks after the treatment decision. Patient questionnaires were used to collect data on sociodemographics, SWTD (primary outcome measure), main treatment goal, DMP, health locus of control (HLoC), and several quality of life (QoL) domains. Predictors of SWTD (6 = worst; 30 = best) were evaluated by uni- and multivariate regression models. Results Of 480 participating patients in eight hospitals and two private practices, 445 completed all questions regarding the primary outcome measure. Forty-five percent of patients preferred shared, while 44 % preferred doctor-directed, decision-making. Median duration of consultation was 30 (range: 10–200) minutes. Overall, 73 % of patients reported high SWTD (≥24 points). In the univariate analyses, global and physical QoL, performance status, treatment goal, HLoC, prognosis, and duration of consultation were significant predictors of SWTD. In the multivariate analysis, the only significant predictor of SWTD was duration of consultation (p = 0.01). Most patients indicated hope for improvement (46 %), followed by hope for longer life (26 %) and better quality of life (23 %), as their main treatment goal. Conclusion Our results indicate that high SWTD can be achieved in most patients with a 30-min consultation. Determining the patient’s main treatment goal and DMP adds important information that should be considered before discussing a new line of palliative treatment.

Long-term outcome of patients with spinal myxopapillary ependymoma: treatment results from the MD Anderson Cancer Center and institutions from the Rare Cancer Network.

BACKGROUND Spinal myxopapillary ependymomas (MPEs) are slowly growing ependymal gliomas with preferential manifestation in young adults. The aim of this study was to assess the outcome of patients with MPE treated with surgery, radiotherapy (RT), and/or chemotherapy. METHODS The medical records of 183 MPE patients (male: 59%) treated at the MD Anderson Cancer Center and 11 institutions from the Rare Cancer Network were retrospectively reviewed. Mean patient' age at diagnosis was 35.5 ± 15.8 years. Ninety-seven (53.0%) patients underwent surgery without RT, and 86 (47.0%) were treated with surgery and/or RT. Median RT dose was 50.4 Gy. Median follow-up was 83.9 months. RESULTS Fifteen (8.2%) patients died, 7 of unrelated cause. The estimated 10-year overall survival was 92.4% (95% CI: 87.7-97.1). Treatment failure was observed in 58 (31.7%) patients. Local failure, distant spinal relapse, and brain failure were observed in 49 (26.8%), 17 (9.3%), and 11 (6.0%) patients, respectively. The estimated 10-year progression-free survival was 61.2% (95% CI: 52.8-69.6). Age (<36 vs ≥36 y), treatment modality (surgery alone vs surgery and RT), and extent of surgery were prognostic factors for local control and progression-free survival on univariate and multivariate analysis. CONCLUSIONS In this series, treatment failure of MPE occurred in approximately one third of patients. The observed recurrence pattern of primary spinal MPE was mainly local, but a substantial number of patients failed nonlocally. Younger patients and those not treated initially with adjuvant RT or not undergoing gross total resection were significantly more likely to present with tumor recurrence/progression.

IMRT credentialing for prospective trials using institutional virtual phantoms: results of a joint European Organization for the Research and Treatment of Cancer and Radiological Physics Center project.

BACKGROUND AND PURPOSE Intensity-modulated radiotherapy (IMRT) credentialing for a EORTC study was performed using an anthropomorphic head phantom from the Radiological Physics Center (RPC; RPC(PH)). Institutions were retrospectively requested to irradiate their institutional phantom (INST(PH)) using the same treatment plan in the framework of a Virtual Phantom Project (VPP) for IMRT credentialing. MATERIALS AND METHODS CT data set of the institutional phantom and measured 2D dose matrices were requested from centers and sent to a dedicated secure EORTC uploader. Data from the RPC(PH) and INST(PH) were thereafter centrally analyzed and inter-compared by the QA team using commercially available software (RIT; ver.5.2; Colorado Springs, USA). RESULTS Eighteen institutions participated to the VPP. The measurements of 6 (33%) institutions could not be analyzed centrally. All other centers passed both the VPP and the RPC ±7%/4 mm credentialing criteria. At the 5%/5 mm gamma criteria (90% of pixels passing), 11(92%) as compared to 12 (100%) centers pass the credentialing process with RPC(PH) and INST(PH) (p = 0.29), respectively. The corresponding pass rate for the 3%/3 mm gamma criteria (90% of pixels passing) was 2 (17%) and 9 (75%; p = 0.01), respectively. CONCLUSIONS IMRT dosimetry gamma evaluations in a single plane for a H&N prospective trial using the INST(PH) measurements showed agreement at the gamma index criteria of ±5%/5 mm (90% of pixels passing) for a small number of VPP measurements. Using more stringent, criteria, the RPC(PH) and INST(PH) comparison showed disagreement. More data is warranted and urgently required within the framework of prospective studies.

IMRT with ¹⁸FDG-PET\CT based simultaneous integrated boost for treatment of nodal positive cervical cancer

BACKGROUND To evaluate toxicity and outcome of intensity modulated radiotherapy (IMRT) with simultaneous integrated boost (SIB) to the positive lymph nodes in patients with loco-regional advanced cervical cancer (LRACC). METHODS The study population comprised ten patients with 18FDG-PET\CT positive lymph nodes (LNs), who underwent chemoradiation with IMRT and SIB. A dose of 50.4 Gy, in daily fractions of 1.8 Gy, was delivered to primary tumor and draining LNs. Primary tumor received an additional external beam boost to a total dose of 55.8 Gy. A SIB of 62 Gy, in daily fractions of 2 Gy, was delivered to the 18FDG-PET\CT positive LNs. Finally, a high dose rate brachytherapy (HDRB) boost (15 - 18 Gy) was administered to the primary tumor. The primary goal of this study was to evaluate acute and early late toxicity and loco-regional control. RESULTS The median number of irradiated LNs per patient was 3 (range: 1-6) with a median middle nodal SIB-volume of 26.10 cm3 (range, 11.9-82.50 cm3). Median follow-up was 20 months (range, 12 to 30 months). Acute and late grade 3 toxicity was observed in 1 patient. Three of the patients developed a recurrence, one in the form of a local tumor relapse, one had a paraaortic LN metastasis outside the treated volume and the last one developed a distant metastasis. CONCLUSION IMRT with SIB in the region of 18FDG-PET positive lymph nodes appears to be an effective therapy with acceptable toxicity and might be useful in the treatment of patients with locally advanced cervical cancer.

Multimodal treatment for high-risk prostate cancer with high-dose intensity-modulated radiation therapy preceded or not by radical prostatectomy, concurrent intensified-dose docetaxel and long-term androgen deprivation therapy: results of a prospective phase II trial.

BACKGROUND The optimal management of high-risk prostate cancer remains uncertain. In this study we assessed the safety and efficacy of a novel multimodal treatment paradigm for high-risk prostate cancer. METHODS This was a prospective phase II trial including 35 patients with newly diagnosed high-risk localized or locally advanced prostate cancer treated with high-dose intensity-modulated radiation therapy preceded or not by radical prostatectomy, concurrent intensified-dose docetaxel-based chemotherapy and long-term androgen deprivation therapy. Primary endpoint was acute and late toxicity evaluated with the Common Terminology Criteria for Adverse Events version 3.0. Secondary endpoint was biochemical and clinical recurrence-free survival explored with the Kaplan-Meier method. RESULTS Acute gastro-intestinal and genito-urinary toxicity was grade 2 in 23% and 20% of patients, and grade 3 in 9% and 3% of patients, respectively. Acute blood/bone marrow toxicity was grade 2 in 20% of patients. No acute grade ≥ 4 toxicity was observed. Late gastro-intestinal and genito-urinary toxicity was grade 2 in 9% of patients each. No late grade ≥ 3 toxicity was observed. Median follow-up was 63 months (interquartile range 31-79). Actuarial 5-year biochemical and clinical recurrence-free survival rate was 55% (95% confidence interval, 35-75%) and 70% (95% confidence interval, 52-88%), respectively. CONCLUSIONS In our phase II trial testing a novel multimodal treatment paradigm for high-risk prostate cancer, toxicity was acceptably low and mid-term oncological outcome was good. This treatment paradigm, thus, may warrant further evaluation in phase III randomized trials.

Is thermochemotherapy with the Synergo system a viable treatment option in patients with recurrent non-muscle-invasive bladder cancer?

OBJECTIVES To prospectively evaluate the outcome of combined microwave-induced bladder wall hyperthermia and intravesical mitomycin C instillation (thermochemotherapy) in patients with recurrent non-muscle-invasive bladder cancer. METHODS Between 2003 and 2009, 21 patients (median age 70 years, range 35-95 years) with recurrent non-muscle-invasive bladder cancer (pTaG1-2 n = 9; pTaG3 n = 3; pT1 n = 9; concurrent pTis n = 8) were prospectively enrolled. Of 21 patients, 15 (71%) had received previous intravesical instillations with bacillus Calmette-Guérin, mitomycin C and/or farmorubicin. Thermochemotherapy using the Synergo system was carried out in 11 of 21 patients (52%) with curative intent, and in 10 of 21 patients (48%) as prophylaxis against recurrence. RESULTS The median number of thermochemotherapy cycles per patient was six (range 1-12). Adverse effects were frequent and severe: urinary urgency/frequency in 11 of 21 patients (52%), pain in eight of 21 patients (38%) and gross hematuria in five of 21 patients (24%). In eight of 21 patients (38%), thermochemotherapy had to be abandoned because of the severity of the adverse effects (pain in 3/8, severe bladder spasms in 2/8, allergic reaction in 2/8, urethral perforation in 1/8). Overall, six of 21 patients (29%) remained free of tumor after a median follow up of 50 months (range 1-120), six of 21 patients (29%) had to undergo cystectomy because of multifocal recurrences or cancer progression and seven of 21 patients (33%) died (2/7 of metastatic disease, 5/7 of non-cancer related causes). CONCLUSIONS Given the high rate of severe side-effects leading to treatment discontinuation, as well as the limited tumor response, thermochemotherapy should be offered only in highly selected cases of recurrent non-muscle-invasive bladder cancer.

Treatment and outcomes of urethral recurrence of urinary bladder cancer in women after radical cystectomy and orthotopic neobladder: a series of 12 cases

INTRODUCTION The incidence, treatment, and outcome of urethral recurrence (UR) after radical cystectomy (RC) for muscle-invasive bladder cancer with orthotopic neobladder in women have rarely been addressed in the literature. PATIENTS AND METHODS A total of 12 patients (median age at recurrence: 60 years) who experienced UR after RC with an orthotopic neobladder were selected for this study from a cohort of 456 women from participating institutions. The primary clinical and pathological characteristics at RC, including the manifestation of the UR and its treatment and outcome, were reviewed. RESULTS The primary bladder tumors in the 12 patients were urothelial carcinoma in 8 patients, squamous cell carcinoma and adenocarcinoma in 1 patient each, and mixed histology in 2 patients. Three patients (25%) had lymph node-positive disease at RC. The median time from RC to the detection of UR was 8 months (range 4-55). Eight recurrences manifested with clinical symptoms and 4 were detected during follow-up or during a diagnostic work-up for clinical symptoms caused by distant metastases. Treatment modalities were surgery, chemotherapy, radiotherapy, and bacillus Calmette-Guérin urethral instillations. Nine patients died of cancer. The median survival after the diagnosis of UR was 6 months. CONCLUSIONS UR after RC with an orthotopic neobladder in females is rare. Solitary, noninvasive recurrences have a favorable prognosis when detected early. Invasive recurrences are often associated with local and distant metastases and have a poor prognosis. © 2014 S. Karger AG, Basel.