Low Back Pain Perceptions and Coping Strategies in Pre-Professional Dancers: A Qualitative Study.

AIMS: Low back pain (LBP) is a common health problem in pre-professional dancers which could hamper the dancers' professional career. However, pre-professional dancers are not often studied, although they may have their own pain perceptions and coping strategies towards LBP. Considering the biopsychosocial nature of LBP, it is important to increase the understanding of these perceptions and coping strategies. The aim of this qualitative research study was to explore the dancers' perceptions about LBP and their coping strategies when they suffered from LBP. METHODS: Eighteen pre-professional dancers with and without LBP from different dance schools in Belgium were included in this study. Participants were invited for an in-depth online video interview. These in-depth interviews were based on a topic list. Afterwards, the interview transcripts were analyzed thematically. RESULTS: Two primary themes emerged from the data: 1) perceptions of LBP and 2) coping strategies which dancers applied when they suffered from LBP. The perceptions about LBP were related to two different themes: "it's all about the body" and "it's all about the psychosocial and contextual factors." In addition, the coping strategies were divided into "active coping strategies" and "passive coping strategies," whereas the most popular coping strategies were stretching exercises and passive coping strategies such as massages or heating cream. CONCLUSION: Although LBP has clearly been shown to be a biopsychosocial phenomenon, this qualitative study showed that dancers mainly considered biomedical factors as contributing factors to LBP. Additionally, instead of relying on coping strategies aimed at directly improving pain or trying to treat LBP on the basis of a single-cause diagnosis, it is important to consider the biopsychosocial origin of LBP in the management plans.

Carboplatin-paclitaxel compared to Carboplatin-Paclitaxel-Bevacizumab in advanced or recurrent endometrial cancer: MITO END-2 - A randomized phase II trial.

OBJECTIVE: Increased Vascular Endothelial Growth Factor Receptor (VEGF) expression in endometrial cancer (EC) is associated with a poor prognosis. Preliminary clinical data reported Bevacizumab effectiveness in EC both as single agent and in combination with chemotherapy. METHODS: In a phase II trial, patients with advanced (FIGO stage III-IV) or recurrent EC were randomized to receive Carboplatin-Paclitaxel standard dose for 6-8 cycles vs Carboplatin-Paclitaxel and Bevacizumab 15 mg/kg in combination with chemotherapy and maintenance until disease progression or unacceptable toxicity. The primary endpoint was progression free survival (PFS). RESULTS: 108 patients were randomized; PFS (10.5 vs 13.7 months, HR 0.84 p = 0.43), overall response rate (ORR 53.1% vs 74.4%) and overall survival (OS) (29.7 vs 40.0 months, HR 0.71 p = 0.24) resulted in a non-significant increase in Bevacizumab treated patients. The PFS increase became significant when an exploratory analysis with the Breslow test was used. Moreover, patients treated with Bevacizumab experienced a significant increase in 6-month disease control rate (70.4% vs 90.7%). Cardiovascular events were more frequent in the experimental arm ("de novo" grade ≥2 hypertension 21% vs 0% and grade ≥2 thromboembolic events 11% vs 2% in the Bevacizumab vs standard treatment arm, respectively). CONCLUSIONS: Bevacizumab combined with chemotherapy in the treatment of advanced/recurrent EC failed to demonstrate a significant increase in PFS in the MITO END-2 trial. Nevertheless, these preliminary data suggests some effectiveness of the antiangiogenic agent which merits further exploration in a larger population with a better molecular characterization.

Conservative surgery in stage I adult type granulosa cells tumors of the ovary: Results from the MITO-9 study.

OBJECTIVE: About 30% of Adult type granulosa cell tumors of the ovary (AGCTs) are diagnosed in fertile age. In stage I, conservative surgery (fertility-sparing surgery, FSS), either unilateral salpingo-oophorectomy (USO) or cystectomy are possible options. The aim of this study is to compare oncological outcomes of FSS and radical surgery (RS) in apparently stage I AGCTs treated within the MITO group (Multicenter Italian Trials in Ovarian cancer). METHODS: Survival curves were calculated using the Kaplan-Meier method and compared with log-rank test. The role of clinicopathological variables as prognostic factors for survival was assessed using Cox's regression. RESULTS: Two-hundred and twenty-nine patients were included; 32.6% received FSS, 67.4% RS. In the FSS group, 62.8% underwent USO, 16.7% cystectomy, 20.5% cystectomy followed by USO. After a median follow up of 84 months, median DFS was significantly worse in the FSS-group (10 yr DFS 50% vs 74%, in FSS and RS group, p = 0.006). No significant difference was detected between RS and USO (10 yr DFS 75% vs 70%, p = 0.5).Cystectomy-group showed a significantly worse DFS compared to USO (10 yr DFS 16% vs 70%, p < 0.001). Patients receiving cystectomy and subsequent USO showed a better prognosis, even though significantly worse compared to USO (10 yr DFS 41% vs 70%, p = 0.05). Between FSS and RS, no difference in OS was detected. At multivariate analysis, FIGO stage IC and cystectomy retained significant predictive value for worse survival. CONCLUSIONS: This study supports the oncological safety of FSS in stage I AGCTs, provided that cystectomy is avoided; USO should be the preferred approach.

Laparoscopic surgery in the treatment of stage I adult granulosa cells tumors of the ovary: Results from the MITO-9 study.

OBJECTIVE: Surgery represents the mainstay of treatment of stage I adult type granulosa cell tumors of the ovary (AGCTs). Because of the rarity and indolent course of the disease, no prospective trials are available. Open surgery has long been considered the traditional approach; oncological safety of laparoscopy is only supported by small series or case reports. The aim of this study was to compare the oncological outcomes between laparoscopic and open surgery in stage I AGCTs treated within the MITO (Multicenter Italian Trials in Ovarian cancer) Group. METHODS: Data from patients with stage I AGCTs were retrospectively collected. Clinicopathological features were evaluated for association with relapse and death. Survival curves were calculated using the Kaplan-Meier method and compared with the log-rank test. The role of clinicopathological variables as prognostic factors for survival was evaluated using Cox's regression model. RESULTS: 223 patients were identified. Stage 1A, 1B and 1C were 61.5%, 1.3% and 29.6% respectively. 7.6% were apparently stage I. Surgical approach was laparoscopic for 93 patients (41.7%) and open for 130 (58.3%). 5-years DFS was 84% and 82%, 10-years DFS was 68% and 64% for the laparoscopic and open-group (p = 0.6).5-years OS was 100% and 99%, 10 years OS was 98% and 97% for the laparoscopic and open-surgery group (p = 0.8). At multivariate analyses stage IC, incomplete staging, site of primary surgery retained significant prognostic value. CONCLUSION: The present study suggests that surgical route does not affect the oncological safety of patients with stage I AGCTs, with comparable outcomes between laparoscopic and open approach.

Quality-of-life analysis of the MITO-8, MaNGO, BGOG-Ov1, AGO-Ovar2.16, ENGOT-Ov1, GCIG study comparing platinum-based versus non-platinum-based chemotherapy in patients with partially platinum-sensitive recurrent ovarian cancer.

Background: MITO-8 showed that prolonging platinum-free interval by introducing non-platinum-based chemotherapy (NPBC) does not improve prognosis of patients with partially platinum-sensitive recurrent ovarian cancer. Quality of life (QoL) was a secondary outcome. Patients and methods: Ovarian cancer patients recurring or progressing 6-12 months after previous platinum-based chemotherapy (PBC) were randomized to receive PBC or NPBC as first treatment. QoL was assessed at baseline, third and sixth cycles, with the EORTC C-30 and OV-28 questionnaires. Mean changes and best response were analysed. Progression-free survival, response rate, and toxicity are also reported for proper interpretation of data. All analyses were based on intention-to-treat. Results: Out of the 215 patients, 151 (70.2%) completed baseline questionnaire, balanced between the arms; thereafter, missing rate was higher in the NPBC arm. At mean change analysis, C30 scores were prevalently worse in the NPBC than PBC arm, statistical significance being attained for emotional functioning, global health status/QoL, fatigue, and dyspnoea (effect sizes ranging from 0.30 to 0.51). Conversely, as for OV28 scale, the other chemotherapy side-effects item was significantly worse with PBC at three and six cycles, with a larger effect size (0.70 and 0.54, respectively). At best response analysis, improvement of emotional functioning and pain and worsening of peripheral neuropathy and other chemotherapy side-effects were significantly more frequent in the PBC arm. Progression-free survival (median 9 versus 5 months, P = 0.001) and objective response rate (51.6% versus 19.4%, P = 0.0001) were significantly better with PBC. Allergy, blood cell count, alopecia, nausea, musculoskeletal, and neurological side-effects were more frequent and severe with PBC; hand-foot skin reaction, rash/desquamation, mucositis, and vascular events were more frequent with NPBC. Conclusion: MITO-8 QoL analysis shows that deterioration of some functioning and symptom scales is lower with PBC, with improvement of emotional functioning and pain, despite worsening of toxicity-related items. ClinicalTrials.gov: NCT00657878.

Perspective: Towards Personalised Metabolic Coaching in Cancer.

Although cancer survivorship has improved over the last decades, numbers of cancer incidence and prevalence are rising. Evidence is growing that lifestyle factors, such as physical activity, a healthy weight management and -diet, play an important role in first- and second line preventive strategies. When implementing a healthy lifestyle, the maintenance of the energy balance should be taken into account. The energy equilibrium is achieved when the energy intake (Ei) for one day is equal to the total daily energy expenditure (TEE). The latter is, among others, made up of the resting energy expenditure, its largest contributor (60-80% of TEE), and can be assessed by indirect calorimetry (i.e. the gold standard). The resting energy expenditure reflects the individual's minimal caloric need in 24h to support basal functions. In cancer patients, energy imbalances, expressed as a positive (Ei > TEE) or negative (Ei & TEE) energy balance, may occur and are characterised by weight gain or -loss respectively. As a corollary, shifts in fatmass and fatfree mass are reported. Adequate nutritional follow-up is necessary in order to meet the energy needs, since both positive and negative energy balances are known to have deteriorating effects on cancer prognosis and mortality. In the clinical setting, predictive formulas (e.g. Harris-Benedict equation) are often used to estimate the caloric need. However, both under- and overfeeding are reported when using equations. Therefore, we advise to use indirect calorimetry in the standard assessment of a patient's energy need in order to provide adequate metabolic coaching and -follow up.

Tertiary cytoreductive surgery in recurrent epithelial ovarian cancer: A multicentre MITO retrospective study.

OBJECTIVES: To evaluate the impact of tertiary cytoreductive surgery (TCS) on survival in recurrent epithelial ovarian cancer (EOC), and to determine predictors of complete cytoreduction. METHODS: A multi-institutional retrospective study was conducted within the MITO Group on a 5-year observation period. RESULTS: A total of 103 EOC patients with a ≥6month treatment-free interval (TFI) undergoing TCS were included. Complete cytoreduction was achieved in 71 patients (68.9%), with severe post-operative complications in 9.7%, and no cases of mortality within 60days from surgery. Multivariate analysis identified the complete tertiary cytoreduction as the most potent predictor of survival followed by FIGO stage I-II at initial diagnosis, exclusive retroperitoneal recurrence, and TCS performed ≥3years after primary diagnosis. Patients with complete tertiary cytoreduction had a significantly longer overall survival (median OS: 43months, 95% CI 31-58) compared to those with residual tumor (median OS: 33months, 95% CI 28-46; p<0.001). After multivariate adjustment the presence of a single lesion and good (ECOG 0) performance status were the only significant predictors of complete surgical cytoreduction. CONCLUSIONS: This is the only large multicentre study published so far on TCS in EOC with ≥6month TFI. The achievement of postoperative no residual disease is confirmed as the primary objective also in a TCS setting, with significant survival benefit and acceptable morbidity. Accurate patient selection is of utmost importance to have the best chance of complete cytoreduction.

5'UTR +24T>C CR2 is not associated with nasopharyngeal carcinoma development in the North Region of Portugal.

OBJECTIVE: We have analysed the association of the +24T>C polymorphism (rs3813946) in CR2, the cellular receptor for Epstein-Barr virus (EBV), in the susceptibility for the development of nasopharyngeal carcinoma (NPC). METHODS: A retrospective case-control study was developed with peripheral blood samples from 111 individuals with NPC and 608 healthy individuals (controls) from the North region of Portugal. The genotyping analysis was performed by allelic discrimination real-time PCR using a TaqMan(®) SNP Genotyping Assay. RESULTS: The genotype distribution was 62.2% TT, 34.2% TC and 3.6% CC for NPC patients; and 65.0%, 30.6% and 4.4%, respectively, for controls. Our study showed no statistical association between the genotype distribution in controls and all types of NPC (P = 0.717); nevertheless, the analysis showed statistically significant differences (P = 0.038) regarding cases with well- or moderately differentiated types of NPC suggesting that +24CC/CT genotypes are associated with increased risk (OR = 4.16; 95% CI 1.28-15.7; P = 0.016). CONCLUSIONS: This is the first study in Western populations to characterize the association of the CR2 +24T>C polymorphism in NPC development, and our results suggest that more studies are required to clarify the impact on NPC susceptibility in different populations.

Effect of different head and neck positions on behaviour, heart rate variability and cortisol levels in lunged Royal Dutch Sport horses.

Different head-and-neck positions (HNPs) are discussed in relation to potential welfare issues. To evaluate the effect on welfare, seven Royal Dutch Sport horses were studied in five predetermined HNPs: (1) unrestrained (HNP1); (2) neck raised, bridge of nose around the vertical (HNP2); (3) neck lowered and considerably flexed, bridge of nose pointing towards the chest (HNP4); (4) neck raised and extended, bridge of nose in front of the vertical (HNP5), and (5) neck lowered and flexed, bridge of nose pointing towards the carpus (HNP7). A standardised exercise test (SET) of 34 min consisted of trot, canter and walk. Behaviour was recorded with a pre-defined ethogram and R-R intervals measured using telemetry. Cortisol concentrations were taken at the start, 5 and 30 min after the SET. Behaviour around the SET was scored separately. Conflict behaviours increased significantly during HNP2 when compared with HNP1, HNP4 and HNP7 during the SET, and there was significant negative anticipation before HNP2 and HNP7. The heart rate variability (HRV) frequency domain for HNP2 showed a significantly increased low frequency peak (LFpeak) compared with other HNPs, and there was a decrease in very low frequency (VLF%) compared with HNP1. HNP4 showed a significant increase in LF% and decrease in VLF% compared with HNP1. Saliva cortisol concentrations were significantly increased in HNP2 at 5 and 30 min after exercise. Increased conflict behaviour was mostly observed in HNP2, but there was a raised HRV suggesting a sympathetic shift in HNP2 and HNP4, and increased cortisol concentrations during HNP2 indicated a stress response.

The role of nt590 P21 gene polymorphism in the susceptibility to nasopharyngeal cancer.

AIM: The purpose of this study was to assess if the P21 nt590 polymorphism is associated with the susceptibility to nasopharyngeal cancer and with the age at diagnosis. MATERIALS AND METHODS: We analyzed the frequency of 3'UTR P21 polymorphisms in blood samples from 102 nasopharyngeal cancer patients and 191 controls, with no known oncologic disease, using PCR-RFLP. RESULTS: The polymorphism genotype frequencies were 93.2% (CC), 5.2% (CT) and 1.6% (TT) in the control group and 88.2% (CC), 10.8% (CT) and 1.0% (TT) in the cases group. We found no statistically significant association between the different P21 polymorphism genotypes and risk of nasopharyngeal cancer (p = 0.201). However, approximately a four-fold increased risk of undifferentiated nasopharyngeal carcinoma in early stages was observed for P21 T carriers (OR = 3.734; 95% IC 1.289-10.281; p = 0.01). Furthermore, our results indicate that the waiting time for onset of neoplasia in T carriers patients was 12.4 years earlier (56.5 years old), comparing with those carrying CC genotype (68.9 years old). CONCLUSIONS: Our findings suggest that the 3'UTR P21 polymorphism may play an important role in the pathogenesis and initiation, but not in the progression, of undifferentiated nasopharyngeal carcinoma. Moreover, the polymorphism seems to contribute to a significantly earlier age at diagnosis.

Laparoscopic surgical staging of endometrial cancer: does obesity influence feasibility and perioperative outcome?

AIM: Laparoscopic treatment of early-stage endometrial cancer is the gold standard to reduce perioperative morbidity. Obesity is a well-known risk factor for endometrial cancer and anesthesiological and surgical complications. The authors' aim was to examine the effect of body mass index (BMI) on perioperative parameters and complications in laparoscopically-treated patients with endometrial cancer. MATERIALS AND METHODS: A consecutive series of patients affected by endometrial cancer and their demographic and clinicopathological data were collected. Patients were divided in 41 non-obese (BMI or= 30) groups. All patients had been preoperatively evaluated with hysteroscopic procedures and toraco-abdominal computed tomography (CT) and had been submitted to laparoscopic radical hysterectomy according to Querleu-Morrow, pelvic lymphadenectomy, peritoneal washing, and bilateral adnexectomy. RESULTS: There was no statistically significant difference in blood loss, number of lymph nodes removed, and hospital stay between the groups, but there was a trend towards a lengthening of surgical time in the obese women. There were no major intraoperative and postoperative complications. DISCUSSION: This study demonstrates that laparoscopic approach is feasible and safe in obese women evaluating the anesthesiological risk.

Morular endometrial metaplasia: review of the literature and proposal of the management.

PURPOSE OF INVESTIGATION: Morular endometrial metaplasia is a rare condition that can be often misdiagnosed and overtreated, because it can be mistaken for a malignant disease. The aim of this review was to update the current opinion on the significance of this pathology and its risk for potential malignancies. MATERIALS AND METHODS: The authors report their experience of two cases of morular metaplasia involving very young women managed conservatively with hysteroscopic resection of the affected areas. RESULTS: Hysteroscopic resection of these lesions can be an adequate and fertility-sparing treatment of morular metaplasia in women of childbearing age. CONCLUSIONS: Morular metaplasia has indeed a mutational origin but it is a benign and hormonally inert condition. The risk to develop cancer is closely associated with premalignant or malignant endometrioid glandular proliferations that are often associated with hysthological finding of morules rather than with morules themselves. Management of this condition requires trained pathologists and gynecologists and should be adapted to the age of the patient.

Long-term follow-up is crucial after treatment for granulosa cell tumours of the ovary.

OBJECTIVE: The aim of this study is to evaluate the long-term outcome of granulosa cell tumour (GCT) of the ovary in a large series of patients treated in MITO centres (Multicentre Italian Trials in Ovarian Cancer) and to define prognostic parameters for relapse and survival. METHODS: A retrospective multi-institutional review of patients with GCTs of the ovary treated or referred to MITO centres was conducted. Surgical outcome, intraoperative and pathological findings and follow-up data were analysed. Kaplan-Meier and Cox proportional hazards analyses were used to determine the predictors for survival and recurrence. RESULTS: A total of 97 patients with primary GCT of the ovary were identified. The median follow-up period was 88 months (range 6-498). Of these, 33 patients had at least one episode of disease recurrence, with a median time to recurrence of 53 months (range 9-332). Also, 47% of recurrences occurred after 5 years from initial diagnosis. At multivariate analysis, age and stage were independent poor prognostic indicators for survival; surgical treatment outside MITO centres and incomplete surgical staging retained significant predictive value for recurrence in both univariate and multivariate analyses. CONCLUSIONS: This study confirms the generally favourable prognosis of GCTs of the ovary, with 5-year overall survival approaching 97%. Nevertheless, prognosis after 20 years was significantly poorer, with 20-year survival rate of 66.8% and a global mortality of 30-35. These findings support the need for lifelong follow-up even in early-stage GCT.

PET/CT in the management of metastatic cervical lymphadenopathy from unknown primary site: a seven years retrospective study.

OBJECTIVES: To evaluate the accuracy of PET/CT for the diagnostic evaluation of patients presenting cervical node metastasis of suspected unknown primary; furthermore to understand its relative clinical utility and relevance when compared to classic endoscopic investigation approach. MATERIALS & METHODS: A retrospective study was pursued, collecting information from clinical files of all patients who presented to the Portuguese Institute of Oncology - Oporto, from January 2005 to December 2011, with cervical node metastases whose primary hadn't been found, despite clinical examination and standard imaging (CT scan or MRI) and therefore were submitted to a PET/CT. Among those presenting with non-supraclavicular metastasis patients were subsequently analyzed according to: histopathology; those who performed examination under anaesthesia (EUA) for biopsies either before of after PET/CT. RESULTS: Eighty nine patients were included in the study. Detection rate was 32.6% with no statistically difference between those with supraclavicular metastases and those with metastases in higher cervical levels (p = 0.24). In this last group (n = 76), 43% patients had had PET/CT and an endoscopy associated with biopsies of the upper aerodigestive tract in different orders, to complete diagnostic workup in cases where the first performed was inconclusive. No statistically difference was found between these two methods (p = 0.25). Most of noticed false negatives were microscopic lesions located deep in the palatine tonsils. CONCLUSIONS: PET/CT showed to be an useful tool when searching for primary tumours whether metastasis were supraclavicular or located in higher levels of the neck. Despite its good accuracy and detection of tumours previously undetected by EUA with biopsies (missed mainly due to sampling error), up-front negative scan shouldn't preclude performing endoscopies. Being evident that both tools are helpful. It was not possible in this study to find any evidence that could show which one of these two exams should be performed first.

A phase I-II study of elacytarabine (CP-4055) in the treatment of patients with ovarian cancer resistant or refractory to platinum therapy.

PURPOSE: Treatment of patients with recurrent ovarian cancer remains a challenge, and there is a need for new and more effective agents. A phase I-II study was designed to determine the recommended dose (RD) and the anti-tumour effect of a prolonged administration of elacytarabine, the elaidic ester of cytarabine, in patients with refractory/resistant recurrent ovarian cancer. EXPERIMENTAL DESIGN: The primary objective of the dose escalation phase I part was to determine the RD for elacytarabine when given twice for five consecutive days in a 4-week schedule, D1-5 and D8(+2)-12(+2) q4w. Three to six patients were to be enrolled at each dose level. The start dose was elacytarabine 75 mg/m(2)/day. The phase II part was designed as a two-step study based on response. RESULTS: A total of 28 patients entered the study, 17 patients in the phase I part and 11(#) patients in phase II. Three dose levels were tested: 75 mg/m(2)/day in 3 patients, 100 mg/m(2)/day in 7 + 11(#) patients, and 125 mg/m(2)/day in 7 patients. Three (17.6%) patients in phase I experienced a dose limiting toxicity (DLT), all at the 125 mg/m(2)/day dose level, establishing the lower dose of 100 mg/m(2)/day as the RD. The DLTs were neutropenia grade 4 according to the Common Terminology Criteria for Adverse Events (CTCAE) and thrombocytopenia grade 4 (2 patients), and vomiting grade 2 with hospitalisation and hypokalaemia grade 3 (1 patient). The best response was a clinically meaningful stabilization observed in 3 patients. In two of them, the disease stabilization exceeded the previous platinum-free interval (PFI). CONCLUSIONS: The RD for elacytarabine was 100 mg/m(2)/day, D1-5 and D8-12 q4w. The safety profile was comparable to the safety profiles reported in previous clinical studies with elacytarabine in solid tumours. Despite some longer-lasting disease stabilisations, two of them exceeding the previous progression-free interval, further investigations of elacytarabine in the ovarian cancer indication are not warranted.

Amino acid profile during exercise and training in Standardbreds.

The objective of this study is to assess the influence of acute exercise, training and intensified training on the plasma amino acid profile. In a 32-week longitudinal study using 10 Standardbred horses, training was divided into four phases, including a phase of intensified training for five horses. At the end of each phase, a standardized exercise test, SET, was performed. Plasma amino acid concentrations before and after each SET were measured. Training significantly reduced mean plasma aspartic acid concentration, whereas exercise significantly increased the plasma concentrations of alanine, taurine, methionine, leucine, tyrosine and phenylalanine and reduced the plasma concentrations of glycine, ornithine, glutamine, citrulline and serine. Normally and intensified trained horses differed not significantly. It is concluded that amino acids should not be regarded as limiting training performance in Standardbreds except for aspartic acid which is the most likely candidate for supplementation.

Evaluation of pemetrexed (Alimta, LY231514) as second-line chemotherapy in persistent or recurrent carcinoma of the cervix: the CERVIX 1 study of the MITO (Multicentre Italian Trials in Ovarian Cancer and Gynecologic Malignancies) Group.

BACKGROUND: The objective of the study was to estimate the antitumor activity of pemetrexed in patients with advanced/recurrent carcinoma of the cervix and to determine the nature and degree of toxicity. METHODS: A multicenter phase II trial was conducted by the Multicentre Italian Trials in Ovarian Cancer and Gynecologic Malignancies (MITO) Group. Patients with advanced/recurrent measurable carcinoma of the cervix that had failed one prior chemotherapy regimen in association or not with radiotherapy were treated with pemetrexed at a dose of 500 mg/m(2) every 21 days. All the patients had a measurable lesion according to RECIST criteria in a not previously irradiated field. RESULTS: From November 2006 to September 2008, 43 patients were entered by seven member institutions of the MITO-Group. A total of 164 cycles (median 2, range 1-9) were administered. The treatment was well tolerated. More serious toxic effects (grades 3 and 4) included leukopenia in 27.9% and neutropenia in 30.2% of patients. No treatment-related deaths were reported. Six patients (13.9%) had partial responses (at least a 30% decrease in the sum of longest diameter of target lesions taking as reference the baseline sum longest diameter) with a median response of 7 weeks (range 3-27). Twenty-three patients (53.4%) had stable disease (less than a 50% reduction and less than a 25% increase in the sum of the products of two perpendicular diameters of all measured lesions and the appearance of no new lesions) and fourteen (32.5%) patients had progressive disease. Median progression-free survival was 10 weeks and overall survival was 35 weeks. CONCLUSION: Pemetrexed showed moderate activity against advanced/recurrent cervical cancer that had failed prior chemotherapy.

Overtrained horses alter their resting pulsatile growth hormone secretion.

The influence of intensified and reduced training on nocturnal growth hormone (GH) secretion and elimination dynamics was studied in young (1.5 yr) Standardbred geldings to detect potential markers indicative for early overtraining. Ten horses trained on a treadmill for 32 wk in age-, breed-, and gender-matched fixed pairs. Training was divided into four phases (4, 18, 6, and 4 wk, respectively): 1) habituation to high-speed treadmill trotting, 2) normal training, in which speed and duration of training sessions were gradually increased, 3) in this phase, the horses were divided into 2 groups: control (C) and intensified trained (IT) group. In IT, training intensity, duration, and frequency were further increased, whereas in control these remained unaltered, and 4) reduced training (RT). At the end of phases 2, 3, and 4, blood was sampled overnight every 5 min for 8 h for assessment of GH secretory dynamics using pulse detection, deconvolution analysis, and approximate entropy (ApEn). Intensified training induced overtraining (performance decreased by 19% compared with C), which was associated with an increase in concentration peaks number (3.6 vs. 2.0, respectively), a smaller peak secretion pattern with a prolonged half-life (15.2 vs. 7.3 min, respectively), and an increased ApEn (0.89 vs. 0.49, respectively). RT did not lead to full recovery for the overtrained horses. The increased irregularity of nocturnal GH pulsatility pattern is indicative of a loss of coordinated control of GH regulation. Longer phases of somatostatin withdrawal are hypothesized to be the underlying mechanism for the observed changes in GH pulsatility pattern.

Carboplatin and pegylated liposomal doxorubicin for advanced ovarian cancer: preliminary activity results of the MITO-2 phase III trial.

BACKGROUND: Based on the efficacy of pegylated liposomal doxorubicin (PLD) in relapsed ovarian cancer, we are conducting a phase III study comparing carboplatin plus either paclitaxel or PLD as first-line therapy in advanced ovarian cancer. Because of limited phase I and II data on PLD plus carboplatin in this setting, we conducted an interim activity analysis. PATIENTS AND METHODS: Patients with stage 1c-IV epithelial ovarian cancer were randomized to carboplatin AUC 5 plus either paclitaxel 175 mg/m(2) or PLD 30 mg/m(2) every 3 weeks for 6 cycles. The interim activity analysis was planned according to a single-stage phase II design with an auspicated 50% response rate; 50 patients eligible for response assessment were required. Response was defined according to RECIST (Response Evaluation Criteria in Solid Tumors). RESULTS: A complete response was achieved in 14 patients (28%) and a partial response in 20 (40%), which produced an overall response rate of 68%. The activity exceeded the minimum required for study continuation. Stable disease was reported in an additional 10 patients (20%). CONCLUSIONS: The adopted schedule of PLD plus carboplatin demonstrates activity as a first-line treatment for advanced ovarian cancer.

Long-term follow-up after cancer rehabilitation using high-intensity resistance training: persistent improvement of physical performance and quality of life.

The short-term beneficial effects of physical rehabilitation programmes after cancer treatment have been described. However, little is known regarding the long-term effects. The purpose of this study was to investigate the long-term effects of high-intensity resistance training compared with traditional recovery. A total of 68 cancer survivors who completed an 18-week resistance training programme were followed for 1 year. During the 1-year follow-up, 19 patients dropped out (14 due to recurrence of cancer). The remaining 49 patients of the intervention group were compared with a group of 22 patients treated with chemotherapy in the same period but not participating in any rehabilitation programme. Outcome measures were muscle strength, cardiopulmonary function, fatigue, and health-related quality of life. One year after completion of the rehabilitation programme, the outcome measures in the intervention group were still at the same level as immediately after rehabilitation. Muscle strength at 1 year was significantly higher in patients who completed the resistance training programme than in the comparison group. High-intensity resistance training has persistent effects on muscle strength, cardiopulmonary function, quality of life, and fatigue. Rehabilitation programmes for patients treated with chemotherapy with a curative intention should include high-intensity resistance training in their programme.