Effect of Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy on Quality of Life in Patients with Peritoneal Mesothelioma.

INTRODUCTION: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) is an accepted treatment for peritoneal mesothelioma. In this study, we evaluated QOL after HIPEC for peritoneal mesothelioma. METHODS: This was a prospective study performed after HIPEC for peritoneal mesothelioma between 2002 and 2015. Patients completed QOL surveys, including the Short Form-36 (SF-36), Functional Assessment of Cancer Therapy + Colon (FACT-C), Brief Pain Inventory (BPI), and Center for Epidemiologic Studies Depression Scale (CES-D) preoperatively and at 3, 6, 12, and 24 months postoperatively. RESULTS: Overall, 46 patients underwent HIPEC for peritoneal mesothelioma and completed QOL surveys. Mean age was 52.8 ± 13.8 years and 52% were male. Good preoperative functional status was 70%. Median survival was 3.4 years, and 1, 3, and 5-year survivals were 77.4, 55.2, and 36.5%, respectively. CES-D score decreased at 3 months postoperatively, but increased at 24 months (p = 0.014); SF-36 physical functioning scale decreased at 3 months but returned to baseline at 12 months (p = 0.0045); and the general health scale decreased at 3 months, then improved by 6 months (p = 0.0034). Emotional well-being (p = 0.0051), role limitations due to emotional problems (p = 0.0006), social functioning (p = 0.0022), BPI (p = 0.025), least pain (p = 0.045), and worst pain (p < 0.0001) improved. FACT-C physical well-being decreased at 3 months but returned to baseline at 6 months (p = 0.020), and total FACT-C score improved at 6 months (p = 0.052). CONCLUSION: QOL returned to baseline or improved from baseline between 3 months and 1 year following surgery. Despite the risks associated with this operation, patients may tolerate HIPEC well and have good overall QOL postoperatively.

Health-Related Quality of Life After Cytoreductive Surgery/HIPEC for Mucinous Appendiceal Cancer: Results of a Multicenter Randomized Trial Comparing Oxaliplatin and Mitomycin.

BACKGROUND: This study evaluated health-related quality of life (HRQOL) using patient-reported outcomes in subjects with mucinous appendiceal neoplasms who underwent cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) as part of a randomized trial comparing mitomycin with oxaliplatin. METHODS: In this prospective multicenter study, 121 mucinous appendiceal cancer patients, with evidence of peritoneal dissemination who underwent CRS, were randomized to receive mitomycin (divided 40 mg) or oxaliplatin (200 mg/m2) for HIPEC. The Functional Assessment of Cancer Therapy Neurotoxicity (FACT-G/NTX) questionnaire was utilized to assess HRQOL. The Trial Outcome Index (TOI) is a summary index responsive to changes in physical/functional outcomes. Repeated measures mixed models with an unstructured variance matrix were applied to assess changes in HRQOL longitudinally. RESULTS: Baseline questionnaire compliance was 95.9%. Baseline physical well-being (PWB) was independently associated with overall survival (hazard ratio 0.79, 95% confidence interval 0.66-0.96; p = 0.017). The TOI was significantly lower in the mitomycin group compared with the oxaliplatin arm at 12 weeks (p = 0.044; score difference 6.35) and 24 weeks after surgery (p = 0.049; score difference 5.61). At 12 weeks after surgery, declines from baseline were significant in the TOI (p = 0.004; score decline 8.99), PWB (p < 0.001; score decline 2.83), and FWB (p < 0.001; score decline 3.42) in the mitomycin group but not the oxaliplatin group. CONCLUSIONS: Compared with mitomycin, HIPEC perfusion with oxaliplatin results in significantly better physical and functional outcomes. With similar survival outcomes and complication rates, oxaliplatin should be considered as the chemoperfusion agent of choice in mucinous appendiceal cancer patients undergoing CRS/HIPEC.

Quality-of-Life Evaluation After Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy.

BACKGROUND: Cytoreductive surgery (CS) with hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal metastases can alleviate symptoms and prolong survival at the expense of morbidity and quality of life (QoL). This study aimed to monitor QoL and outcomes before and after HIPEC. METHODS: A prospective QoL trial of patients who underwent HIPEC for peritoneal metastases from 2000 to 2015 was conducted. The patients completed the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36), the Functional Assessment of Cancer Therapy + Colon Subscale (FACT-C), the Brief Pain Inventory, the Center for Epidemiologic Studies Depression scale, and the Eastern Cooperative Oncology Group (ECOG) performance status at baseline, then 3, 6, 12, and 24 months after HIPEC. The trial outcome index (TOI) was analyzed. Proportional hazards modeled the effect of baseline QoL on survival. RESULTS: The 598 patients (53.8 % female) in the study had a mean age of 53.3 years. The overall 1-year survival rate was 76.8 %, and the median survival period was 2.9 years. The findings showed a minor morbidity rate of 29.3 %, a major morbidity rate of 21.7 %, and a 30-day mortality rate of 3.5 %. The BPI (p < 0.0001) and worst pain (p = 0.004) increased at 3 months but returned to baseline at 6 months. After CS + HIPEC, FACT-C emotional well-being, SF-36 mental component score, and emotional health improved (all p < 0.001). Higher baseline FACT-General (hazard ratio [HR], 0.92; 95 % confidence interval [CI], 0.09-0.96), FACT-C (HR, 0.73; 95 % CI 0.65-0.83), physical well-being (HR, 0.71; 95 % CI 0.64-0.78), TOI (HR, 0.87; 95 % CI 0.84-0.91), and SF-36 vitality (HR, 0.88; 95 % CI 0.83-0.92) were associated with improved survival (all p < 0.001). Higher baseline BPI (HR, 1.1; 95 % CI 1.05-1.14; p < 0.0001), worst pain (HR, 1.06; 95 % CI 1.01-1.10; p = 0.01), and ECOG (HR, 1.74; 95 % CI 1.50-2.01; p < 0.0001) were associated with worse survival. CONCLUSIONS: Although HIPEC is associated with morbidity and detriments to QoL, recovery with good overall QoL typically occurs at or before 6 months. Baseline QoL is associated with morbidity, mortality, and survival after HIPEC.

Predicting postoperative morbidity following cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CS+HIPEC) with preoperative FACT-C (Functional Assessment of Cancer Therapy) and patient-rated performance status.

BACKGROUND: Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CS+HIPEC) is associated with significant perioperative morbidity. One goal of our ongoing patient-reported health-related quality of life (HRQoL) program is to describe the prognostic value of HRQoL measures for predicting postoperative morbidity and mortality following CS+HIPEC. METHODS: A retrospective analysis of a prospectively collected clinical database for all patients treated for peritoneal carcinomatosis and who participated in our patient-reported HRQoL program from 2001 to 2011 was done. Patients completed the Functional Assessment of Cancer Therapy questionnaire plus the colon symptom subscale, in addition to the Eastern Cooperative Oncology Group (ECOG) performance status rating prior to CS+HIPEC. The trial outcome index (TOI), a specific measure of function, symptoms, and physical well being of the patient, was analyzed. The TOI is a combination of the physical and functional well being subscales + the colon-specific subscale of the FACT-C. RESULTS: Of 855 patients, 387 (45.2 %) participated in the HRQoL trials. Mean age was 53.3 years, and 213 (55 %) were female versus 174 (45 %) males. There were 240 patients (62 %) who had a complication versus 147 (38 %) who had no complication. A 30-day mortality rate of 7.7 % (30) was documented. Patients who suffered a 30-day postoperative mortality demonstrated a lower mean preoperative score in the FACT-C TOI 52.7 versus 61.7; P < 0.001. Independent predictors of 30-day mortality on multivariate analysis included TOI (0.05), age (0.001), and smoking (0.001). Patients with a higher TOI score were less likely to suffer a mortality (95 % CI 0.9-1.0, P = 0.05). Patients with a higher emotional well being (EWB) score were less likely to suffer a complication 0.9 (95 % CI 0.87-1.0, P = 0.04). Other independent predictors of postoperative morbidity included diabetic status (P = 0.05), ECOG performance status (0.001), and gender (0.02). CONCLUSIONS: Preoperative HRQoL, as measured by FACT-C and ECOG performance status and added to traditional factors, helps predict postoperative morbidity and mortality following CS+HIPEC.

Quality of life and survival in advanced cervical cancer: a Gynecologic Oncology Group study.

PURPOSE: To determine associations between pretreatment health-related quality of life subscales with progression-free (PFS) and overall survival (OS) in advanced and recurrent cervical cancer. PATIENTS AND METHODS: Patients included those participating in Gynecologic Oncology Group advanced or recurrent cervical cancer phase III treatment trials who completed the Functional Assessment of Cancer Therapy for patients with cervical cancer (FACT-Cx) and a single-item pain scale at study entry. The FACT-Cx includes five domains: physical (PWB), emotional (EWB), social (SWB), functional well being (FWB), and cervix cancer subscale (CCS). A high quality of life (QoL) score reflects better QoL. After stratifying by protocol and adjusting for patient and disease characteristics, a Cox proportional hazards model was fitted for each subscale as a continuous variable. If statistically significant, (p<0.05), an analysis on mean item scores (MIS) was performed. RESULTS: Nine-hundred-ninety-one patients were enrolled from 1997 to 2007. The majority (87%) had recurrent disease. After adjustment for covariates and predictors, only the PWB domain (better physical QoL) was associated with improved OS [HR 0.96 95% CI 0.95-0.98; p<0.001]. When classifying patients based on the MIS of each subscale, the patients with the lowest risk of death were likely to report less compromised QoL (MIS>3) for PWB [HR 0.44 (0.33-0.58) P<0.001], FWB [0.49 (0.38-0.62) P<0.001], and CCS [0.48 (0.38-0.61) P<0.001]. CONCLUSION: The pretreatment patient-reported PWB as measured by the PWB subscale of the FACT-Cx, is significantly associated with survival in advanced cervical cancer trials, even after controlling for known prognostic factors.

A phase II trial of thalidomide and procarbazine in adult patients with recurrent or progressive malignant gliomas.

Thalidomide and procarbazine have demonstrated single agent activity against malignant gliomas (MG). We evaluated the combination of thalidomide and procarbazine with a single arm phase II trial in adults with recurrent or progressive MG. Procarbazine was given at a dose of 250 mg/m(2)/d × 5day q 28 days. Thalidomide was administered at a dose of 200 mg/day continuously. Intrapatient dose escalation of thalidomide was attempted (increase by 100 mg/day weekly as tolerated) to a maximum of 800 mg/day. The primary outcome was tumor response, assessed by MRI and CT. Secondary outcomes were progression free survival (PFS), overall survival (OS) and toxicity. In addition, quality of life questionnaires were performed at baseline and prior to each odd cycle in all treated patients. Eighteen patients (median age of 50) were accrued and received a total of 36 cycles (median 2) of therapy. The median maximum thalidomide dose achieved was 400 mg (range 0-800). No complete or partial responses were seen. One patient (6%) experienced stable disease, fourteen (78%) progressed as best response and three (17%) were not evaluable for response. Median time to progression was 2.1 months (95% CI, 1.5-2.5). Seventeen patients have died (one patient lost to follow-up after progression); median survival from enrollment was 7.6 months (95% CI, 3.5-9.4). Grade 3/4 drug related toxicity was minimal. Quality of life diminished over time. The combination of thalidomide and procarbazine demonstrated no efficacy in this trial.

Patient rated outcomes and survivorship following cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy (CS + HIPEC).

BACKGROUND: Cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy (CS + HIPEC) is a treatment combining cytoreductive surgery with hyperthermic chemotherapy directly into the peritoneal cavity. Recipients may gain extended life when compared with best supportive care; yet results often are achieved with substantial morbidity and health-related quality of life (HRQOL) deficits. The purpose of this study was to record patient rated outcomes and the HRQOL of long-term survivors. METHODS: One hundred and two patients living 12+ months post-treatment completed a survey including the Medical Outcomes Study 36-item Short Form Health Survey (SF-36), Functional Assessment of Cancer Therapy-Colon (FACT-C), and Pittsburgh Sleep Quality Index. RESULTS: SF-36 Physical Component scores were significantly lower than general population norms (46.7, z= -2.943, P=0.003), while Mental Component scores were significantly higher (53.6, z=4.208, P ≤ 0.001). FACT scores were higher than general FACT normative scores. The majority (56%) of these survivors reported significant sleep quality impairment. CONCLUSION: Although most HRQOL scores were comparable to or higher than those of the general population, long-term physical and functional deficits remain. These deficits, along with the poor sleep quality of recipients, may be improved by survivorship programs or targeted psychosocial interventions.

Survival and quality of life following cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy for peritoneal carcinomatosis of colonic origin.

BACKGROUND: Peritoneal carcinomatosis of colonic origin (PCC) is a life-threatening diagnosis. Cytoreductive surgery (CS) with hyperthermic intraperitoneal chemotherapy (HIPEC) offers patients the prospect of long-term survival with alleviation of symptoms. METHODS: Patients underwent HIPEC for PCC and completed questionnaires preoperatively (T1) and after surgery at 3 (T2), 6 (T3), and 12 (T4) months. Questionnaires included the Functional Assessment of Cancer Therapy-Colon (FACT-C), Brief Pain Inventory (BPI), SF-36 Medical Outcomes Study Survey (SF-36), Center for Epidemiologic Studies-Depression Scale (CES-D), and the ECOG Performance Status Rating. RESULTS: A total of 62 patients were assessed before surgery. Median overall survival was 18 months, with 71.3 ± 6.3% survival at 1 year. Emotional well-being (P = .0007) improved after HIPEC. Social/family well-being (P = .065) and the colon subscale (P = .061) of the FACT worsened at T2, but recovered by T3. One-third to one-half of patients reported depressive symptoms over the course of the study. Pain scores increased above BL at T2, but decreased below BL at T3 and T4. CONCLUSIONS: Emotional well being is improved after CS + HIPEC despite complications that may affect short-term recovery. Most patients remaining in the study recover to preoperative levels of functioning between 3 and 6 months after surgery. For some, survival can be attained without major decrement in QOL at 1 year. QOL concerns must be a key component in the evaluation for patients with PCC for CS and HIPEC.

Caregiver Quality of Life Before and After Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.

BACKGROUND: Cytoreductive surgery plus intraperitoneal hyperthermic chemotherapy (CRS+HIPEC) is a formidable procedure, often affecting the quality of life (QOL) of the caregiver as well as the patient. We explored the impact of quality of life and depressive symptom burdens of CRS+HIPEC caregivers prospectively. STUDY DESIGN: Patient and caregiver dyads were both consented per IRB-approved protocol; CRS ± HIPEC was performed. The impact on QOL and depressive symptom burdens was assessed on patient-caregiver dyads via the Caregiver Quality of Life (CG QOL-C), CES-D (Center for Epidemiological Studies - Depression) instruments; pre-CS+HIPEC (T1), postoperative (T2), 6 (T3), and 12 (T4) months. RESULTS: Seventy-seven dyads were approached, with 73 participating. Both caregiver and patient depressive symptom trajectories changed significantly. CES-D means for caregivers were (T1-4): 15.1 (SE [standard error] 1.7), 15.0 (1.4), 10.3 (1.4), 13.1 (2.1), p = 0.0008; for patients were: 10.3 (SE 1.1), 13.7 (1.4), 9.0 (1.2), and 10.3 (1.5), p = 0.0002. Preoperatively, caregivers scored 4.8 points (SD 13.4) (p = 0.026) higher than patients. Patients experienced an increase in depression scores at the postoperative visit. At T3, both groups dropped to less concerning levels; yet caregiver CES-D scores increased again at T4 4.7 points (SD 12.5) higher than the patients, and financial well-being became worse from T1 to T3. Possible, probable, and "cases" of depression were higher for caregivers were at all measured time points. CONCLUSIONS: Significant numbers of caregivers endured high depressive symptom burdens and financial concerns. Different caregiver-patient trajectories reflect the need for differential timing of supportive interventions. Evaluation of quality of life and impact of CRS+HIPEC procedures must move beyond assessment of only the patient.

Goals and Adverse Effects: Rate of Concordance Between Patients and Providers.

PURPOSE: Adequate understanding of the goals and adverse effects of cancer treatment has important implications for patients' decision making, expectations, and mood. This study sought to identify the degree to which patients and clinicians agreed upon the goals and adverse effects of treatment (ie, concordance). METHODS: Patients completed a demographic questionnaire, the National Comprehensive Cancer Network Distress Thermometer, the Medical Outcomes Study Social Support Survey, the Functional Assessment of Chronic Illness Therapy-Treatment Satisfaction-General questionnaire, the Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being questionnaire, and a 13-item questionnaire about the goals and adverse effects of treatment. Providers completed a 12-item questionnaire. RESULTS: One hundred patients (51 female) and 34 providers participated (questionnaire return rate mean difference, 5 days; SD, 16 days). Patient and provider dyads agreed 61% of the time regarding the intent of treatment. In cases of nonagreement, 36% of patients reported more optimistic therapy goals compared to providers. Patients and providers agreed 69% of the time regarding the patient's acknowledgement and understanding of adverse effects. Patients who reported an understanding of likely adverse effects endorsed significantly lower distress scores (mean, 2.5) than those who endorsed not understanding associated adverse effects (mean, 4.1; P = .008). CONCLUSION: Timely data capturing of patient-provider dyadic ratings is feasible. A significant discrepancy exists between a substantial percentage of patients' and providers' views of the intent and adverse effects of treatment. Patients were almost always more optimistic about the intent of treatment. Higher rates of distress were noted in cases of discordance. Providers may benefit from conversational feedback from patients as well as other integrated feedback systems to inform them about patient understanding.

Survival and health outcomes after cytoreductive surgery with intraperitoneal hyperthermic chemotherapy for disseminated peritoneal cancer of appendiceal origin.

BACKGROUND: Cytoreductive surgery with intraperitoneal hyperthermic chemotherapy for peritoneal carcinomatosis of appendiceal origin can alleviate symptoms and prolong survival. This aggressive therapy may impair patient quality of life (QOL). The purpose of this study was to monitor health outcomes before and after treatment. METHODS: Patients underwent cytoreductive surgery and intraperitoneal hyperthermic chemotherapy for peritoneal cancer. Patients completed questionnaires consisting of demographic information and the Functional Assessment of Cancer Therapy, the SF-36 Medical Outcomes Study survey, the Center for Epidemiologic Studies-Depression Scale, and the ECOG Performance Status Rating before (T1) and after surgery at 3 (T2), 6 (T3), 12 (T4), and 24 (T5) months. Time trends were assessed with the mixed model (SAS PROC MIXED) to allow use of all the observed data as well as to account for missing data. RESULTS: Fifty-eight patients (50% female) with a mean age 52.4 years (SD 12.6; range, 28-80) were assessed before surgery. Overall survival at 1 year was 78.7%. Emotional well-being improved over the study period, while physical well-being and physical functioning declined at T2 and then improved to near baseline levels at T3 and T4. Percentage of patients with depressive symptoms was as follows: T1 = 24%, T2 = 30%, T3 = 24%, and T4 = 33%. QOL scores improved over time. CONCLUSIONS: Although complications can affect short-term recovery, survival in appendix cancer patients with peritoneal cancer is good and for some can be achieved without major decrements in QOL at 1 year. Depressive symptoms and some physical limitations remain in surviving patients.

Quality of life and nutritional assessment in peritoneal surface malignancy (PSM): recommendations for care.

Quality of life (QOL) and nutritional status of patients treated for peritoneal surface malignancy are important areas for ongoing assessment. A working group of clinicians including a dietitian, physicians, and quality of life researchers was formed as part of the Fifth International Workshop on Peritoneal Surface Malignancy. The purpose of the group was to form a consensus statement on both quality of life and nutritional assessment in PSM. The relevant literature from the quality of life and nutritional assessment in peritoneal surface malignancy was reviewed and integrated to form a consensus statement. Baseline and ongoing assessment of both quality of life and nutritional status of patients undergoing cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy (HIPEC) is recommended.

A phase III, double-blind, placebo-controlled prospective randomized clinical trial of d-threo-methylphenidate HCl in brain tumor patients receiving radiation therapy.

PURPOSE: The quality of life (QOL) and neurocognitive function of patients with brain tumors are negatively affected by the symptoms of their disease and brain radiation therapy (RT). We assessed the effect of prophylactic d-threo-methylphenidate HCl (d-MPH), a central nervous system (CNS) stimulant on QOL and cognitive function in patients undergoing RT. METHODS AND MATERIALS: Sixty-eight patients with primary or metastatic brain tumors were randomly assigned to receive d-MPH or placebo. The starting dose of d-MPH was 5 mg twice daily (b.i.d.) and was escalated by 5 mg b.i.d. to a maximum of 15 mg b.i.d. The placebo was administered as one pill b.i.d. escalating three pills b.i.d. The primary outcome was fatigue. Patients were assessed at baseline, the end of radiation therapy, and 4, 8, and 12 weeks after brain RT using the Functional Assessment of Cancer Therapy with brain and fatigue (FACIT-F) subscales, as well as the Center for Epidemiologic Studies Scale and Mini-Mental Status Exam. RESULTS: The Mean Fatigue Subscale Score at baseline was 34.7 for the d-MPH arm and 33.3 for the placebo arm (p = 0.61). At 8 weeks after the completion of brain RT, there was no difference in fatigue between patient groups. The adjusted least squares estimate of the Mean Fatigue Subscale Score was 33.7 for the d-MPH and 35.6 for the placebo arm (p = 0.64). Secondary outcomes were not different between the two treatment arms. CONCLUSIONS: Prophylactic use of d-MPH in brain tumor patients undergoing RT did not result in an improvement in QOL.

Phase III study of cisplatin with or without paclitaxel in stage IVB, recurrent, or persistent squamous cell carcinoma of the cervix: a gynecologic oncology group study.

PURPOSE: To determine whether cisplatin plus paclitaxel (C+P) improved response rate, progression-free survival (PFS), or survival compared with cisplatin alone in patients with stage IVB, recurrent, or persistent squamous cell carcinoma of the cervix. PATIENTS AND METHODS Eligible: patients with measurable disease, performance status (PS) 0 to 2, and adequate hematologic, hepatic, and renal function received either cisplatin 50 mg/m2 or C+P (cisplatin 50 mg/m2 plus paclitaxel 135 mg/m2) every 3 weeks for six cycles. Tumor measurements and quality-of-life (QOL) assessments were obtained before each treatment cycle. RESULTS: Of 280 patients entered, 6% were ineligible. Among 264 eligible patients, 134 received cisplatin and 130 received C+P. Groups were well matched with respect to age, ethnicity, PS, tumor grade, disease site, and number of cycles received. The majority of all patients had prior radiation therapy (cisplatin, 92%; C+P, 91%). Objective responses occurred in 19% (6% complete plus 13% partial) of patients receiving cisplatin versus 36% (15% complete plus 21% partial) receiving C+P (P = .002). The median PFS was 2.8 and 4.8 months, respectively, for cisplatin versus C+P (P < .001). There was no difference in median survival (8.8 months v 9.7 months). Grade 3 to 4 anemia and neutropenia were more common in the combination arm. There was no significant difference in QOL scores, although a disproportionate number of patients (cisplatin, n = 50; C+P, n = 33) dropped out of the QOL component, presumably because of increasing disease, deteriorating health status, or early death. CONCLUSION C+P is superior to cisplatin alone with respect to response rate and PFS with sustained QOL.

Clinical significance of a NAD(P)H: quinone oxidoreductase 1 polymorphism in patients with disseminated peritoneal cancer receiving intraperitoneal hyperthermic chemotherapy with mitomycin C.

Recent data indicate that NAD(P)H: quinone oxidoreductase 1 (NQO1) is important in the activation of mitomycin C. A polymorphism in human NQO1 (609C>T) is associated with diminished NQO1 activity. The purpose of our study was to determine the effect of the 609C>T polymorphism on tumor NQO1 activity and overall survival in patients with disseminated peritoneal cancer receiving intraperitoneal mitomycin C therapy. Patients with disseminated peritoneal cancer of gastrointestinal or other origin were eligible. Following aggressive surgical debulking, patients were administered a 2-h heated (40.5 degrees C) intraperitoneal perfusion with mitomycin C. NQO1 activity was determined in tumor tissue obtained during surgery and patients were genotyped for the NQO1 C609T polymorphism using a polymerase chain reaction-based method. The major response variable monitored during the trial was overall survival. Of the 117 patients genotyped for the NQO1 609C>T polymorphism, 67% were wild-type (WT), 31% were heterozygous (HE), and 2% were homozygous mutant (HM). In tumor tissue, the mean NQO1 activities from WT (n = 14) and HE (n = 5) patients were 794 +/- 603 and 70 +/- 133.1 nmol/min/mg protein respectively (P = 0.006). Significant differences in survival between WT versus HE/HM genotypes were noted in optimally debulked patients (R0/R1) (43.6+ months, median not yet reached versus 23 months respectively, P = 0.037) and in patients with peritoneal carcinomatosis of colonic origin (18.2 versus 11.5 months respectively, P = 0.050). These data indicate that the NQO1 609C>T polymorphism results in significantly reduced tumor NQO1 activity and reduced survival in subsets of patients receiving intraperitoneal hyperthermic mitomycin C therapy.

Supportive use of megestrol acetate (Megace) with head/neck and lung cancer patients receiving radiation therapy.

PURPOSE: The purpose of this study was to measure the effect of megestrol acetate (MA) on weight loss and quality of life (QOL) in patients with cancer of the lung or head and neck undergoing curative radiation therapy. METHODS AND MATERIALS: This was a Phase III, placebo-controlled, double-blind randomized study. Patients received either 800 mg/day of MA (20 milliliters po qAM) or placebo over a 12-week period. Patients received radiation of the head and neck or thorax using a dose of at least 50 Gy, either alone or with chemotherapy. Weight was assessed weekly, whereas QOL was assessed at baseline and at 4, 8, and 12 weeks. RESULTS: Patient characteristics on the MA arm (16 lung, 12 head/neck; mean age: 60 years) were similar to those on the placebo arm (17 lung, 11 head/neck; mean age: 65.8 years). Patients in the MA group had a mean weight loss over 12 weeks of 2.7 pounds, whereas the placebo group had a mean weight loss of 10.6 pounds. There was a significant time by treatment interaction (p = 0.001), with the difference in weight between treatment groups being most pronounced after 6 weeks. Although overall QOL was similar in both arms of the study, several QOL subscale items did differ significantly. Compared to the placebo-treated patients, head-and-neck cancer patients in the MA arm reported the ability to eat as much as they liked (p = 0.02 at 12 weeks), and lung cancer patients in the MA arm reported significantly better appetite at 4 weeks (p = 0.03) and 8 weeks (p = 0.001). CONCLUSION: MA used prophylactically is useful as an appetite stimulant; it can help patients maintain weight over the course of curative radiotherapy of the head and neck or lung and can improve specific aspects of QOL.

Factors predicting survival after intraperitoneal hyperthermic chemotherapy with mitomycin C after cytoreductive surgery for patients with peritoneal carcinomatosis.

HYPOTHESIS: Certain clinicopathologic factors predict improved survival after cytoreductive surgery and intraperitoneal hyperthermic chemotherapy for peritoneal carcinomatosis. DESIGN: Prospective clinical trial. SETTING: Surgical oncology service at a university academic hospital. PATIENTS: A population of 109 consecutive patients with peritoneal carcinomatosis treated between December 1991 and November 1997. INTERVENTION: All patients underwent resection of gross disease followed by 2-hour intraoperative perfusion of mitomycin C (20-40 mg) into the peritoneal cavity at a temperature of 40.5 degrees C. MAIN OUTCOME MEASURES: Clinicopathologic factors that independently predicted improved overall survival rates. RESULTS: Overall survival at 1 and 3 years was 61% and 33%, respectively. With median follow-up of 52 months, median overall survival was 16 months. Four factors were significant independent predictors of improved survival by multivariate analysis: nonadenocarcinoma histologic features (P =.001), the appendix as a primary site (P =.003), the absence of hepatic parenchymal metastases (P =.01), and complete resection of all gross disease (R1/0 resection) (P<.001). Patients with an R1/0 resection vs an incomplete resection of gross disease (R2 resection) had 3-year overall survival of 68% vs 21% (P<.001). CONCLUSIONS: Patients with peritoneal carcinomatosis have a uniformly poor prognosis. However, in select patients, the natural history of this disease condition may be altered by using the multimodality approach of cytoreductive surgery and intraperitoneal hyperthermic chemotherapy. These results require confirmation in prospective randomized studies.

Cytoreductive surgery with intraperitoneal hyperthermic chemotherapy for advanced gastric cancer.

Peritoneal carcinomatosis is a common and universally fatal sequelae of gastric carcinoma. Treatment of peritoneal carcinomatosis from appendiceal and colorectal sources with intraperitoneal hyperthermic chemotherapy (IPHC) combined with aggressive cytoreductive surgery has been shown to be effective. There are few data on this treatment modality for carcinoma of the stomach. This study evaluates cytoreductive surgery and IPHC with peritoneal carcinomatosis from gastric carcinoma. Thirty-four patients with peritoneal carcinomatosis due to gastric carcinoma underwent gastric resection with cytoreductive surgery followed by IPHC with mitomycin C. A control group consisting of 40 contemporaneous patients, who underwent radical gastrectomy without extended nodal resection, was identified through the tumor registry. Despite more advanced disease in the IPHC group compared to the control group (P < 0.001), overall survival in the two groups was similar. Proportional-hazards regression analysis shows that only resection status is significantly correlated with improved survival (P=0.0068). Within the IPHC group, patients who underwent an R0/R1 resection had increased survival times (11.2 vs. 3.3 months, P=0.015) vs. those who underwent R2 resection. The group who had an R0/R1 resection had 1- and 2-year survival rates of 45% and 45% compared to 16% and 8%, respectively, in the R2 group. Cytoreductive surgery and IPHC is a modality with limited potential for the treatment of peritoneal carcinomatosis from gastric carcinoma. Careful patient selection for this procedure is imperative, and patients in whom an R0/R1 resection can be achieved are the best candidates.

The process of advance care planning in HCT candidates and proxies: self-efficacy, locus of control, and anxiety levels.

The purpose of this study was to examine the relationship between hematopoietic cell transplant candidate and proxy advance care planning (ACP) behavior and attitudes. A total of 49 candidates and 44 proxies completed the Advance Directive Attitudes Survey, Multidimensional Health Locus of Control Scale, Family Decision Making Self-Efficacy Scale, and the State-Trait Anxiety Inventory. In all, 45% of candidates reported completing an advance directive (AD), while only 26% had ADs on file; 80% of candidates discussed ACP wishes with their loved ones and 15% discussed ACP wishes with their medical team. The AD completers were significantly (1) older, (2) more positive about ADs, and (3) were less likely to believe that health events happen by chance. Discrepancies between reported ACP behavior and communication with health care practitioners have implications for end-of-life care.

Measuring meaning and peace with the FACIT-spiritual well-being scale: distinction without a difference?

The Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being Scale (FACIT-Sp; Peterman, Fitchett, Brady, Hernandez, & Cella, 2002) has become a widely used measure of spirituality; however, there remain questions about its specific factor structure and the validity of scores from its separate scales. Specifically, it remains unclear whether the Meaning and Peace scales denote distinct factors. The present study addresses previous limitations by examining the extent to which the Meaning and Peace scales relate differentially to a variety of physical and mental health variables across 4 sets of data from adults with a number of chronic health conditions. Although a model with separate but correlated factors fit the data better, discriminant validity analyses indicated limited differences in the pattern of associations each scale showed with a wide array of commonly used health and quality-of-life measures. In total, the results suggest that people may distinguish between the concepts of Meaning and Peace, but the observed relations with health outcomes are primarily due to variance shared between the 2 factors. Additional research is needed to better understand the separate and joint role of Meaning and Peace in the quality of life of people with chronic illness.