Circadian variation in muscle force output in males using isokinetic, isometric dynamometry: can we observe this in multi-joint movements using the muscleLab force-velocity encoder and are they similar in peak and magnitude?

We have investigated the magnitude of circadian variation in Isokinetic and Isometric strength of the knee extensors and flexors, as well as back squat and bench press performance using the MuscleLab force velocity transducer. Ten resistance-trained males (mean±SD: age 21.5 ± 1.1 years; body mass 78.3 ± 5.2 kg; height 1.71 ± 0.07 m) underwent a) three to four familiarization sessions on each dynamometer and b) four sessions at different times of day (03:00, 09:00, 15:00 and 21:00 h). Each session was administered in a counterbalanced order and included a period when Perceived onset of mood states (POMS), then rectal and muscle temperature (Trec, Tm) was measured at rest, after which a 5-min standardized 150 W warm-up was performed on a cycle ergometer. Once completed, Isokinetic (60 and 240°·s-1 for extension and flexion) and Isometric dynamometry with peak torque (PT), time-to-peak-torque (tPT) and peak force (PF) and % activation was measured. Lastly, Trec and Tm were measured before the bench press (at 30, 50 and 70 kg) and back squat (at 40, 60 and 80 kg) exercises. A linear encoder was attached to an Olympic bar used for the exercises and average force (AF), peak velocity (PV) and time-to-peak-velocity (tPV) were measured (MuscleLab software; MuscleLab Technology, Langesund, Norway) during the concentric phase of the movements. Five-min recovery was allowed between each set with three repetitions being completed. General linear models with repeated measures and cosinor analysis were used to analyse the data. Values for Trec and Tm at rest were higher in the evening compared to morning values (Acrophase Φ: 16:35 and 17:03 h, Amplitude A: 0.30 and 0.23°C, Mesor M: 36.64 and 37.43°C, p < 0.05). Vigor, happy and fatigue mood states responses showed Φ 16:11 and 16:03 h and 02:05 h respectively. Circadian rhythms were apparent for all variables irrespective of equipment used where AF, PF and PT values peaked between 16:18 and 18:34 h; PV, tPV and tPT peaked between 05:54 and 08:03 h (p < 0.05). In summary, circadian rhythms in force output (force, torque, power, and velocity) were shown for isokinetic, isometric dynamometers and complex multi-joint movements (using a linear encoder); where tPV and tPT occur in the morning compared to the evening. Circadian rhythms in strength can be detected using a portable, low-cost instrument that shows similar cosinor characteristics as established dynamometers. Hence, muscle-strength can be measured in a manner that is more directly transferable to the world of athletic and sports performance.

A Phase II Basket Trial of Dual Anti-CTLA-4 and Anti-PD-1 Blockade in Rare Tumors (DART SWOG 1609 Cohort 47) in Patients with Gestational Trophoblastic Neoplasia.

PURPOSE: The efficacy of immune checkpoint blockade in gestational trophoblastic neoplasia (GTN) remains uncertain. We report the results of the GTN cohort of SWOG S1609 dual anti-CTLA-4 and anti-PD-1 blockade in rare tumors (DART). PATIENTS AND METHODS: This prospective, open-label phase II trial evaluated ipilimumab plus nivolumab across multiple rare tumor cohorts, including GTN. Eligible patients received nivolumab 240 mg, i.v. every 2 weeks and ipilimumab 1 mg/kg i.v. every 6 weeks. The primary endpoint was overall response rate [ORR; complete response (CR) + partial response (PR)] by quantitative serum beta human chorionic gonadotropin (ß-hCG); secondary endpoints included progression-free survival (PFS), overall survival (OS), and toxicity. RESULTS: Four patients with refractory GTN enrolled and received therapy. At 11 months of ongoing follow-up, 3 of 4 patients responded [ORR = 75% (CR, 25%, n = 1, tumor mutation burden = 1 mutation/megabase; PD-L1 tumor proportion score = 50%); PR, 50%, n = 2)]. Responders included malignant gestational trophoblastic neoplasm (n = 1, CR, PFS 11+ months) and choriocarcinoma (n = 2, both PRs, PFS 10+ and 6+ months). One patient with epithelioid trophoblastic tumor experienced disease progression. The 6-month PFS was 75% [95% confidence interval (CI), 43%-100%], and the median PFS was not reached (range, 35-339+ days); all 4 patients were alive at last follow-up. Two patients experienced grade 3 immune-related toxicity (arthralgia and colitis); there were no grade ≥4 events. CONCLUSIONS: Ipilimumab plus nivolumab demonstrated efficacy in chemotherapy-refractory GTN, an ultra-rare cancer affecting young women. Three of 4 patients achieved ongoing objective responses with a reasonable safety profile at 6-11+ months.

Distress among African American and White adults with cancer in Louisiana.

Purpose/Objectives: Screening for distress is a key priority in cancer care, and African American patients may experience increased distress compared to White patients. However, this question has not yet been addressed in Louisiana. The purpose of the present study was to examine the relationship between African American race and distress at a cancer center in Louisiana.Design/Methods: This was a retrospective study of 1,544 patients who were treated at an academic cancer center in 2015. Extracted data included patient self-reports of distress using the single-item Distress Thermometer (DT) and demographic and clinical characteristics. Hypotheses were tested using logistic regression.Findings: Distress was present in 19.7% of the sample. In univariate analyses, African American patients were more likely than White patients to experience distress (OR = 1.38, p = .013). However, race was no longer associated with distress in a multivariate analysis that adjusted for the covariates of age, gender, cancer site, presence of metastases, and number of distress screenings (OR = 1.07, p = .670). Distress was more common in patients who were younger (OR = 2.26, p < .001), diagnosed with lung/bronchus cancer (OR = 5.28, p < .001), or screened more often (OR = 5.20, p < .001). Distress was less common among patients with female breast cancer (OR = 0.39, p = .015).Conclusions/Implications: This study suggests that African American individuals with cancer in Louisiana are at increased risk for distress, but that this can be attributed to African American patients being younger, more likely to have lung cancer, and screened more frequently. Implications include careful consideration of patient race, age, and cancer site during distress management in cancer care.

Social support in cancer: How do patients want us to help?

Objective: Social support is fundamentally important to the well-being of patients with cancer, and informal caregivers often wish they had better insight into how to help. The aims of this study were to quantify the types of social support that patients qualitatively expressed as important, and examine whether demographics and mental health symptoms explained the type of support desired. Methods: A sample of 82 patients with cancer (Gender: 65.9% Male, Age: M = 57.5, Race/Ethnicity: 90.2% White, non-Latino/a) completed measures of demographics, health, anxiety, and depression, and responded to an open-ended question asking them to list three types of support that they desire from their caregivers. These responses were then reliably coded into 18 different categories. Results: Most commonly, participants expressed a desire for companionship (45%). Other common requests included empathy (33%), home care support (28%), information support (16%), being treated the same (15%), and help with appointments (13%). Patients who were more anxious were more likely to desire companionship (OR = 4.41, p = .033), and younger patients were more likely to desire home care support (OR = 7.24, p = .016). Conclusion: Findings have implications for providing individually-tailored social support to patients with cancer.

Is the diurnal variation in muscle force output detected/detectable when multi-joint movements are analysed using the musclelab force-velocity encoder?

We have investigated the magnitude of diurnal variation in back squat and bench press performance using the MuscleLab force velocity transducer. Thirty resistance-trained males (mean ± SD: age 21.7 ± 1.4 years; body mass 80.5 ± 4.5 kg; height 1.79 ± 0.06 m) underwent two sessions at different times of day: morning (M, 07:30 h) and evening (E, 17:30 h). Each session included a period when rectal temperature (Trec) was measured at rest, a 5-min standardized 150 W warm-up on a cycle ergometer, then defined programme of bench press (at 20, 40 and 60 kg) and back squat (at 30, 50 and 70 kg) exercises. A linear encoder was attached to an Olympic bar used for the exercises and average force (AF), peak velocity (PV) and time-to-peak velocity (tPV) were measured (MuscleLab software; MuscleLab Technology, Langesund, Norway) during the concentric phase of the movements. Values for Trec at rest were higher in the evening compared to morning values (0.48°C, P < 0.0005). Daily variations were apparent for both bench press and back squat performance for AF (1.9 and 2.5%), PV (8.3 and 12.7%) and tPV (-16.6 and -9.8%; where a negative number indicates a decrease in the variable from morning to evening). There was a main effect for load where AF and tPV increased and PV decreased from the lightest load to the heaviest for both bench press and back squat (47.1 and 80.2%; 31.7 and 57.7%; -42.1 and -73.9%; P < 0.0005 where a negative number indicates a decrease in the variable with increasing load). An interaction was found only for tPV, such that the tPV occurs earlier in the evening than the morning at the highest loads (60 and 70 kg) for both bench press and back squat, respectively (mean difference of 0.32 and 0.62 s). In summary, diurnal variation in back squat and bench press was shown; and the tPV in complex multi-joint movements occurs earlier during the concentric phase of exercise when back squat or bench press is performed in the evening compared to the morning. This difference can be detected using a low cost, portable and widely available commercial instrument and enables translation of past laboratory/tightly controlled experimental research in to main-stream coaching practice.

Cognitive function during and six months following chemotherapy for front-line treatment of ovarian, primary peritoneal or fallopian tube cancer: An NRG oncology/gynecologic oncology group study.

OBJECTIVES: Changes in cognitive function have been identified in and reported by many cancer survivors. These changes have the potential to impact patient quality of life and functional ability. This prospective longitudinal study was designed to quantify the incidence of change in cognitive function in newly diagnosed ovarian cancer patients throughout and following primary chemotherapy. METHODS: Eligible patients had newly diagnosed, untreated ovarian cancer and had planned to receive chemotherapy. Web-based and patient reported cognitive assessments and quality of life questionnaires were conducted prior to chemotherapy, prior to cycle four, after cycle six, and six months after completion of primary therapy. RESULTS: Two-hundred-thirty-one evaluable patients entered this study between May 2010 and October 2011. At the cycle 4 time point, 25.2% (55/218) of patients exhibited cognitive impairment in at least one domain. At the post-cycle 6 and 6-month follow up time points, 21.1% (44/208) and 17.8% (30/169) of patients, respectively, demonstrated impairment in at least one domain of cognitive function. There were statistically significant, but clinically small, improvements in processing speed (p<0.001) and attention (p<0.001) but not in motor response time (p=0.066), from baseline through the six-month follow up time period. CONCLUSIONS: This was a large, prospective study designed to measure cognitive function in ovarian cancer. A subset of patients had evidence of cognitive decline from baseline during chemotherapy treatment in this study as measured by the web-based assessment; however, changes were generally limited to no more than one domain.

Pelvic pleomorphic rhabdomyosarcoma presenting as oliguria in a 61-year-old woman.

Rhabdomyosarcomas (RMSs) are malignant soft-tissue tumors arising from skeletal muscle progenitor cells. They are most commonly diagnosed in children and adolescents and are rare in adults. These tumors arise from a variety of anatomical sites, including the head and neck, urogenital tract, and extremities. Classification of RMSs depends on histopathologic and immunohistochemical features. Embryonal and alveolar subtypes are more common in children and adolescents, whereas the pleomorphic subtype is seen almost exclusively in adults. Adult RMS is associated with poor outcomes and high recurrence rate. Because of the low incidence of adult RMS, most published reports of RMS in adults are either case series or retrospective analyses, and most treatment protocols are extrapolated from clinical trials performed in children. The present report describes a 61-year-old woman with RMS whose presentation included atypical symptoms.

Trocar Site Metastasis Following Robotic Oophorectomy for Ovarian Cancer: A Case Report and Review of the Literature.

While robotic surgery has seen much success in the treatment of gynecologic malignancies, the technical aspects of this approach raise concern for spreading tumor cells within the peritoneal cavity and to trocar sites. To date, robotic trocar site metastases have been identified following surgery for both endometrial and cervical cancer.

Does lowering evening rectal temperature to morning levels offset the diurnal variation in muscle force production?

Muscle force production and power output in active males, regardless of the site of measurement (hand, leg, or back), are higher in the evening than the morning. This diurnal variation is attributed to motivational, peripheral, and central factors and higher core and, possibly, muscle temperatures in the evening. This study investigated whether decreasing evening resting rectal temperatures to morning values, by immersion in a water tank, leads to muscle force production and power output becoming equal to morning values in motivated subjects. Ten healthy active males (mean ± SD: age, 22.5 ± 1.3 yrs; body mass, 80.1 ± 7.8 kg; height, 1.72 ± 0.05 m) completed the study, which was approved by the local ethics committee of the university. The subjects were familiarized with the techniques and protocol and then completed three sessions (separated by at least 48 h): control morning (07:30 h) and evening (17:30 h) sessions (with an active 5-min warm-up on a cycle ergometer at 150 W) and then a further session at 17:30 h but preceded by an immersion in cold water (~16.5 °C) to lower rectal temperature (Trec) to morning values. During each trial, three measures of grip strength, isokinetic leg strength measurements (of knee flexion and extension at 1.05 and 4.19 rad s(-1) through a 90° range of motion), and three measures of maximal voluntary contraction (MVC) on an isometric dynamometer (utilizing the twitch-interpolation technique) were performed. Trec, rating of perceived exertion (RPE), and thermal comfort (TC) were also measured after the subjects had reclined for 30 min at the start of the protocol and prior to the measures for grip, isokinetic, and isometric dynamometry. Muscle temperature was taken after the warm-up or water immersion and immediately before the isokinetic and MVC measurements. Data were analyzed using general linear models with repeated measures. Trec values were higher at rest in the evening (by 0.37 °C; p < 0.05) than the morning, but values were no different from morning values immediately after the passive pre-cooling. However, Trec progressively decreased throughout the experiments, this being reflected in the subjects' ratings of thermal comfort. Muscle temperatures also displayed significant diurnal variation, with higher values in the evening (by 0.39 °C; p < 0.05). Right grip strength, isometric peak power, isokinetic knee flexion and extension for peak torque and peak power at 1.05 rad s(-1), and knee extension for peak torque at 4.19 rad s(-1) all showed higher values in the evening (a range of 3-14%), and all other measures of strength or power showed a statistical trend to be higher in the evening (0.10 > p > 0.05). Pre-cooling in the evening significantly reduced force or power variables towards morning values. In summary, effects of time of day were seen in some measures of muscle performance, in agreement with past research. However, in this population of motivated subjects, there was evidence that decreasing evening Trec to morning values by coldwater immersion decreased muscle strength to values similar to those found in the morning. It is concluded that diurnal changes in muscle performance are linked to diurnal changes in Trec.

Does raising morning rectal temperature to evening levels offset the diurnal variation in muscle force production?

Muscle force production and power output in active males, regardless of the site of measurement (hand, leg, or back), are higher in the evening than in the morning. This diurnal variation is attributed to motivational, peripheral and central factors, and higher core and, possibly, muscle temperatures in the evening. This study investigated whether increasing morning rectal temperatures to evening resting values, by active or passive warm-ups, leads to muscle force production and power output becoming equal to evening values in motivated subjects. Ten healthy active males (mean ± SD: age, 21.2 ± 1.9 yrs; body mass, 75.4 ± 8 kg; height, 1.76 ± .06 m) completed the study, which was approved by the University Ethics Committee. The subjects were familiarized with the techniques and protocol and then completed four sessions (separated by at least 48 h): control morning (07:30 h) and evening (17:30 h) sessions (with an active 5-min warm-up) and then two further sessions at 07:30 h but proceeded by an extended active or passive warm-up to raise rectal temperature to evening values. These last two sessions were counterbalanced in order of administration. During each trial, three measures of handgrip strength, isokinetic leg strength measurements (of knee flexion and extension at 1.05 and 4.19 rad.s(-1) through a 90° range of motion), and four measures of maximal voluntary contraction (MVC) on an isometric ergometer (utilizing the twitch-interpolation technique) were performed. Rectal and intra-aural temperatures, ratings of perceived exertion (RPE) and thermal comfort (TC) were measured. Measurements were made after the subjects had reclined for 30 min and after the warm-ups and prior to the measurement of handgrip and isokinetic and isometric ergometry. Muscle temperature was taken after the warm-up and immediately before the isokinetic and MVC measurements. Warm-ups were either active (cycle ergometer at 150 W) or passive (resting in a room at 35 °C, relative humidity 45%). Data were analyzed using analysis of variance models with repeated measures. Rectal and intra-aural temperatures were higher at rest in the evening (.56 °C and .74 °C; p < .05) than in the morning, but there were no differences after the active or passive warm-ups, the subjects' ratings of thermal comfort reflecting this. Muscle temperatures also displayed significant diurnal variation, with higher values in the evening (~.31 °C; p < .05). Grip strength, isokinetic knee flexion for peak torque and peak power at 1.05 rad.s(-1), and knee extension for peak torque at 4.19 rad.s(-1) all showed higher values in the evening. All other measures of strength or power showed a trend to be higher in the evening ( .10 > p > .05). There was no significant effect of active or passive warm-ups on any strength or power variable, and subjects reported maximal values for effort for each strength measure. In summary, effects of time of day were seen in some measures of muscle performance but, in this population of motivated subjects, there was no evidence that increasing morning rectal temperature to evening values by active or passive warm-up increased muscle strength to evening values.

Extraperitoneal metastases from recurrent ovarian cancer.

OBJECTIVES: To identify patterns of metastasis in patients with recurrent ovarian cancer. The influence of the route of chemotherapy administration and sequence of agents on those patterns is also examined. METHODS: A total of 233 women were treated for primary and secondary recurrences after a diagnosis of stage III ovarian cancer. As initial treatment, all underwent optimal debulking surgery followed by combined intraperitoneal/intravenous (IP) chemotherapy with cisplatin/paclitaxel (99 of the 233 women) or intravenous (IV) carboplatin/paclitaxel (134 of the 233 women). Recurrent disease was then treated with either carboplatin with or without liposomal doxorubicin (CLD) or bevacizumab (BEV). The data were reviewed and the types of treatment, sites of metastasis, and timing of recurrence are described. RESULTS: Thirty-five subjects developed extraperitoneal recurrent ovarian cancer, with 26 subjects (74%) after IP treatment, and 9 subjects (26%) after IV treatment. Of these extraperitoneal recurrences, 26 were in the thoracic/pulmonary cavity, 7 were within the central nervous system (CNS), and 2 were in the cutaneous tissues. The CNS and cutaneous lesions were secondary recurrences, and all occurred in subjects who had initially received IP cisplatin/paclitaxel followed by IV BEV for recurrent disease. CONCLUSIONS: Extraperitoneal recurrences were more common in women treated with IP chemotherapy for ovarian cancer. Specifically, women treated with IV BEV as secondary therapy after IP were at particularly high risk of extraperitoneal metastases, including in the CNS and cutaneous tissues. Physicians should be aware of the possibility of unusual metastases after the combination of IP chemotherapy and BEV, and future prospective studies of this population should carefully evaluate recurrence site patterns.

Embryonal rhabdomyosarcoma: adjuvant and ex vivo assay-directed chemotherapy.

The aim of this retrospective study was to evaluate differences in treatment of embryonal rhabdomyosarcoma (RMS) of the uterus in 2 premenopausal women. We discuss adjuvant chemotherapy and use of ChemoFx Assay (Precision Therapeutics, Pittsburgh, PA) to guide choice of active chemotherapeutic agents. Two premenopausal patients were identified with a pathologic diagnosis of embryonal RMS of the uterus. Both met inclusion criteria for the study. A 21-year-old woman underwent a staging abdominal hysterectomy for a variant of embryonal RMS. Vincristine, actinomycin D, and cyclophosphamide were given adjunctively for a complete response. A 20-year-old woman underwent a diagnostic dilation and curettage revealing embryonal RMS. Initial treatment included an abdominal hysterectomy and nodal sampling. Presentation to a subsequent gynecologic oncologist 7 months later revealed recurrence. Carboplatin, doxorubicin, and paclitaxel provided a partial response. After a second surgical resection, ChemoFx Assay identified ifosfamide and mitomycin C as active agents and resulted in a complete response. Recommended treatment includes surgery and chemotherapy with possible radiation therapy if deemed necessary. The benefit of adding neoadjuvant or adjuvant chemotherapy and radiation therapy allows for a conservative surgical approach and improved survival. Choosing active chemotherapy agents can be aided by ChemoFx Assay. The chemotherapy most commonly used for treatment of embryonal RMS is a combination of vincristine, actinomycin D, and cyclophosphamide.

Factors affecting the completion of intraperitoneal chemotherapy in women with ovarian cancer.

HYPOTHESIS: The use of intraperitoneal (IP) chemotherapy as treatment for ovarian cancer has been demonstrated to result in improved survival. However, it is associated with significant toxicity, resulting in the early discontinuation of therapy in many cases. This report quantifies and analyzes the reasons why patients discontinue therapy before completion and discusses strategies for improvement. METHODS: One hundred seventy-seven women with ovarian cancer who received IP chemotherapy for a 10-year period at a regional cancer center were followed, and demographic and treatment data were collected. SigmaStat (v2.0) was used to make statistical calculations regarding the data. RESULTS: One hundred seventy-seven subjects received 915 cycles of IP therapy. One hundred forty subjects received IP chemotherapy as initial treatment. Ninety-five (68%) of the 140 subjects completed 6 planned cycles. Thirty-seven subjects received IP for recurrent disease. Only 14 (38%) of the 37 subjects completed 6 cycles (P = 0.001). The most common reason for noncompletion of IP therapy was port occlusion (39/68 of the patients, 57%). Very few subjects refused treatment (9/68 of the patients, 13%). The rate of completion of therapy improved over time in this program (2001, 36%; 2009, 75%). CONCLUSIONS: The rate of completion of IP chemotherapy was higher in this institution than in other reports, including randomized multicenter trials. Port occlusion was the most common reason why IP chemotherapy was not completed. Subjective reasons for stopping therapy were rare. The establishment of a comprehensive, coordinated IP administration program is likely to result in improved completion rates. Completion rates within an institution improve with experience as well.

Impact of shifting from office- to hospital-based treatment facilities on the administration of intraperitoneal chemotherapy for ovarian cancer.

INTRODUCTION: Cancer chemotherapy in the United States has been delivered mostly in an office-based setting since the late 1980s. However, in the past 5 years, more patients have been treated in hospitals as a result of reimbursement changes. Intraperitoneal (IP) chemotherapy for ovarian cancer has been similarly affected. This report examines changes in care of women treated with IP chemotherapy in an office- versus hospital-based setting. METHODS: Over 10 years, 140 women with ovarian cancer were identified as candidates for IP chemotherapy. Of these patients, 92 were treated in an oncology-dedicated infusion center in the office of a physicians' group; 48 were treated in a local hospital. Location was determined based on insurance coverage and reimbursement. Data collected included demographics, number of treatment cycles completed, length of each treatment, and adverse events. RESULTS: The age and ethnicity of patients treated in the office versus hospital were similar. All six doses of intravenous IP chemotherapy were completed by 73 (79%) of 92 patients treated in the office versus 23 (48%) of 48 patients treated in the hospital (P < .001). The time of each infusion was longer in the hospital-versus office-based setting (P < .001). There were more adverse events associated with treatment in the hospital. CONCLUSION: IP chemotherapy is associated with worse outcomes in the hospital- compared with office-based setting. The reason seems to involve a relative lack of resources directed specifically to chemotherapy administration. If current reimbursement trends continue, this could result in decreased survival for women with ovarian cancer.

Southwest Oncology Group Trial S9912: intraperitoneal cisplatin and paclitaxel plus intravenous paclitaxel and pegylated liposomal doxorubicin as primary chemotherapy of small-volume residual stage III ovarian cancer.

OBJECTIVE: While primary cisplatin-based intraperitoneal chemotherapy has been shown to favorably impact survival in small-volume residual advanced ovarian cancer, there is a need to develop strategies that improve the effectiveness of this approach. METHODS: A multi-center phase 2 trial was conducted that added intravenous pegylated liposomal doxorubicin (day 8; 30-40 mg/m(2)) to a regimen of intraperitoneal cisplatin (day 2; 75 mg/m(2)) and intravenous (day 1; 135 mg/m(2)) plus intraperitoneal (day 8; 60 mg/m(2)) paclitaxel. Treatment was initially delivered on an every 3-week schedule, but was modified to an every 4-week program due to excessive toxicity. Patients were to receive 6 cycles of this regimen. RESULTS: Of 68 patients entering this trial, 63 patients were eligible and evaluable, of whom 39 (62%) completed 6 cycles. Overall, 32 (51%) experienced at least 1 grade 4 or worse toxicity (most commonly hematologic) including 5 treatment-related deaths. Median progression-free survival (PFS) was 25 months (2-year PFS: 52%) and median overall survival 51 months, an outcome similar to previous reports of cisplatin-based intraperitoneal chemotherapy in comparable patient populations. Seventeen patients (27% of all eligible patients) were without evidence of disease recurrence >4 years following entry into the trial. CONCLUSION: Both the overall trial outcome, and specifically the excessively severe systemic toxicity of this regimen would prevent its future development in this exact form. The provocative PFS in a subset of individuals should encourage the development of alternative strategies designed to optimize the delivery of regional therapy in ovarian cancer management.

Clinical trial participation is associated with improved outcome in women with ovarian cancer.

OBJECTIVES: To determine the effect of participation in clinical trials on survival of women with ovarian cancer. Disease-specific factors and demographics were also examined. METHODS: A total of 158 women were treated for ovarian cancer at a regional cancer center. All patients were offered treatment with surgery/chemotherapy and were screened at diagnosis for participation in clinical research. Progression-free and overall survival, as well as demographic- and treatment-related data, were recorded. RESULTS: Fifty-three participated in clinical trials and 105 did not. On-study versus off-study subjects were similar in age (64.1 vs 63.5 years), ethnicity (87% vs 85% white), performance status (100% 0-1 Gynecologic Oncology Group scale), and urban versus rural lifestyle (58% vs 55% urban). Stage of disease, histologic subtype, and type/amount of therapy were also similar. Kaplan-Meier analysis showed superior overall survival for on-study subjects (median, 46 vs 25 months, 95% confidence interval, 1.0299-2.1505 months, P = 0.0343). A trend toward improved progression-free survival approached significance for on-study subjects (median, 23 vs 9 months, 95% confidence interval, 0.9545-2.0022 months, P = 0.0866). CONCLUSIONS: Women with ovarian cancer who participate in clinical trials at this institution have improved survival compared with those who are treated with standard therapies. No other factors examined were associated with treatment completion or survival. Further, participation in clinical research does not vary by age, ethnicity, urban versus rural lifestyle, or cancer stage or histologic subtype. However, disclosure of this information to potential clinical trial participants may represent an ethical conflict and should be carefully considered in light of existing ethical guidelines for human subject research.

Phase II evaluation of neoadjuvant chemotherapy and debulking followed by intraperitoneal chemotherapy in women with stage III and IV epithelial ovarian, fallopian tube or primary peritoneal cancer: Southwest Oncology Group Study S0009.

OBJECTIVE: Intraperitoneal (IP) chemotherapy prolongs survival in optimally reduced ovarian cancer patients. For patients in whom optimal debulking cannot be achieved, one could incorporate IP therapy post-operatively if the cancer was optimally debulked following neoadjuvant chemotherapy. We sought to evaluate overall survival (OS), progression-free survival (PFS), percent of patients optimally debulked and toxicity in patients treated with this strategy. METHODS: Women with adenocarcinoma by biopsy or cytology with stage III/IV (pleural effusions only) epithelial ovarian, fallopian tube or primary peritoneal carcinoma that presented with bulky disease were treated with neoadjuvant intravenous (IV) paclitaxel 175 mg/m2 and carboplatin AUC 6 q 21 daysx3 cycles followed by surgery (if >/=50% decrease in CA125). If optimally debulked they received IV paclitaxel 175 mg/m2 and IP carboplatin AUC 5 (day 1) and IP paclitaxel 60 mg/m2 (day 8) q 28 daysx6 cycles. RESULTS: Sixty-two patients were registered. Four were ineligible. Fifty-six were evaluated for neoadjuvant chemotherapy toxicities. One patient died of pneumonia. Five patients had grade 4 toxicity, including neutropenia (3), anemia, leukopenia, anorexia, fatigue, muscle weakness, respiratory infection, and cardiac ischemia. Thirty-six patients had debulking surgery. Two had grade 4 hemorrhage. Twenty-six patients received post-cytoreduction chemotherapy. Four had grade 4 neutropenia. At a median follow-up of 21 months, median PFS is 21 months and median OS is 32 months for all 58 patients. PFS and OS for the 26 patients who received IV/IP chemotherapy is 29 and 34 months respectively. CONCLUSIONS: These results compare favorably with other studies of sub-optimally debulked patients.