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Introduction. An at least 3-month expected survival is a common inclusion criterion in cancer treatment trials, including advanced pancreatic cancer phase III studies. Published survival curves for advanced pancreatic cancer however seem to reflect a substantial survival shortfall. We wanted to assess the strength of this observation and search for an explanation by reviewing the literature. Methods. A Medline and EMBASE search was done for chemotherapy or chemotherapy based phase III studies in advanced pancreatic cancer published since 1997. Similar search was done at the American Society's of Clinical Oncology web site for abstracts presented since 2000. Three months mortality was based on the survival curves presented. Results. Fourteen papers and five abstracts met our criteria and are included in our review. Six thousand two hundred and twelve patients participated in these trials and 1 447 (23.3%) died in the first 3-month period. Figures were worse in patients with metastases and poorer performance status. Assuming that most deaths during treatment happened during the first 3-months, cause of death was reported in only 40 cases (2.8%). Progressive cancer was reported as cause of death in 21 of these cases. Less frequent causes of death were reported to be infections, 'complications of cancer', thromboembolic events and renal failure. Discussion. Overall treatment-related deaths represent a very small percentage of the deaths happening during the 3-month period, and are unlikely to be under-reported given the Good Clinical Practice oversight of these trials. Progressive cancer is likely to be an important cause of early mortality but given the very select nature of the trial-related population this cannot explain the phenomenon of 3-month early death burden of 23.3%. Our hypothesis, supported by multiple autopsy series, is that early death burden in advanced pancreatic cancer trial patients is likely to be due to under-reported vascular thromboembolic events. Thromboprophylaxis needs to be addressed in future trials. [ABSTRACT FROM AUTHOR]

Background and objectives. Cancer-related cognitive impairment has been acknowledged as a substantial limiting factor in quality of life among cancer patients and survivors. In addition to deficits on behavioral measures, abnormalities in neurologic structure and function have been reported. In this paper, we review findings from the literature on cognitive impairment and cancer, potential interventions, meditation and cognitive function, and meditation and cancer. In addition, we offer our hypotheses on how meditation practice may help to alleviate objective and subjective cognitive function, as well as the advantages of incorporating a meditation program into the treatment of cancer patients and survivors for cancer-related cognitive deficits. Findings. Various factors have been hypothesized to play a role in cancer-related cognitive impairment including chemotherapy, reduced hormone levels, proinflammatory immune response, fatigue, and distress. Pharmacotherapies such as methylphenidate or modafinil have been suggested to alleviate cognitive deficits. While initial reports suggest they are effective, some pharmacotherapies have side effects and may not relieve other symptoms associated with multimodal cancer treatment including sleep disturbance, nausea and pain. Several recent studies investigating the effects of meditation programs have reported behavioral and corresponding neurophysiological modulations that may be particularly effective in alleviating cancer-related cognitive impairment. Such programs also have been shown to reduce stress, fatigue, nausea and pain, and improve mood and sleep quality. Conclusions. With the increasing success of cancer treatment and the ability to return to previous family, social, and work activities, symptom management and quality of life are an essential part of survivorship. We propose that meditation may help to improve cancer-related cognitive dysfunction, alleviate other cancer-related sequelae, and should be fully investigated as an adjuvant to cancer treatment. [ABSTRACT FROM AUTHOR]

This paper deals with some of the musculo-skeletal complication that can occur after cancer treatment. In particular, we focus on Cancer Treatment Induced Bone Loss (CTIBL) and the musculo-skeletal complications that can occur in patients treated for extremity sarcoma. In addition we discuss peripheral neuropathy, musculo-skeletal pain and briefly mention some of the complications related to radiotherapy. CTIBL is mostly studied in breast cancer and prostate cancer survivors. The cause in these groups is mainly due to treatment induced hypogonadism. Other causes of CTIBL are indirect or direct cause of chemotherapy, physical inactivity and inadequate intake of vitamin D and calcium. Treatment of CTIBL consists of diet and lifestyle changes and pharmacological intervention. Extremity bone sarcomas constitute a special group since they often experience mutilating surgery and heavy combination chemotherapy. The treatment results in worse function than the normal population and the amputated usually have lower physical functioning than patients treated with limb sparing surgery (LSS). However, most studies fail to show differences in quality of life between the amputated and LSS. Most of the studies performed on musculo-skeletal sequelae have been done on survivors of childhood cancer, breast cancer or prostate cancer. More studies among the other cancer groups are needed to reveal the extent and prevalence of these complications. [ABSTRACT FROM AUTHOR]

Background. The benefit of adjuvant therapy for resected small bowel adenocarcinoma has not been proven. We undertook a retrospective analysis to evaluate the benefit of adjuvant therapy in a clearly defined patient population with curatively resected small bowel adenocarcinoma. Material and methods. We identified 54 patients with small bowel adenocarcinoma who underwent margin-negative surgical resection and were evaluated after surgery at the University of Texas, M. D. Anderson Cancer Center between 1990 and 2008. Disease-free survival (DFS) and overall survival (OS) were estimated. Results. Median age was 55 years and primary tumor site was duodenum in 67%, jejunum in 20%, and ileum in 13%. Thirty patients (56%) received adjuvant therapy consisting of systemic chemotherapy with or without radiation in 28 and radiation alone in two. Patients who received adjuvant therapy had significantly higher tumor stage and rate of lymph node involvement. Five-year DFS and OS did not differ between treatment groups. In multivariate analysis, the use of adjuvant therapy was associated with improved DFS (HR 0.27; 95% CI 0.07–0.98, P = 0.05) but not OS (HR 0.47; 95% CI 0.13–1.62, P = 0.23). In patients with a high risk of relapse (defined as a lymph node ratio ≥10%), adjuvant therapy appeared to improve OS, P = 0.04, but not DFS, P = 0.15. Discussion. The use of adjuvant therapy for curatively resected small bowel adenocarcinoma was associated with an improvement in DFS. This finding strongly supports further investigation of adjuvant chemotherapy in this tumor type. [ABSTRACT FROM AUTHOR]

Introduction. The aim of this retrospective analysis was to analyze the results of conventional radical radiotherapy in the treatment of oropharyngeal cancer and to identify pre-treatment and treatment-related prognostic factors for outcome. Material and methods. The records of 627 patients with oropharyngeal cancer treated with radical radiotherapy with conventional techniques were analyzed. Results. The median age was 56 years. History of tobacco abuse was present in 80.5%. Eighty six percent had stage III or IV disease. Radical radiotherapy alone was the treatment modality for 71.2% and concomitant or neoadjuvant chemotherapy was used in 28.8%. The 3-year local control (LC), loco-regional control (LRC), disease-free survival (DFS) and overall survival (OS) was 49%, 40.6%, 38.9% and 36.1% respectively. The 3-year DFS rates were 80.3% for stage I, 65.8% for stage II, 46.1% for stage III and 25.2% for stage IV disease. Multivariate analysis was performed for prognostic factors. Prior history of tobacco abuse was an independent prognostic factor for both DFS and LRC. Karnofsky Performance Score (KPS) < 80, higher nodal stage, lower total radiotherapy dose (<66 Gy) in those receiving > 60 Gy, and overall treatment time > 50 days were other independent prognostic factors for inferior DFS and LRC. KPS < 80, higher T stage, higher nodal stage, RT dose < 66 Gy and longer overall treatment time (>50 days) were independent prognostic factors for poorer local control. Conclusions. Several patient-, disease- and treatment-related variables independently affect survival outcomes after radical radiotherapy for oropharyngeal cancer. Oropharyngeal cancers in those without a history of tobacco abuse may be biologically different and more amenable to cure with radiotherapy. [ABSTRACT FROM AUTHOR]

Nasopharyngeal carcinoma (NPC) is a rare disease in Sweden. For evaluation of the treatment outcomes in our NPC patients, 52 new cases that were referred to our department between 1991 and 2002 were retrospectively analysed. Tumor stage, according to the 1997 AJCC staging system, was I in five, II in ten, III in 12 and IV in 25 patients. Majority of the patients (87%) had World Health Organization type II-III tumors. Neoadjuvant chemotherapy was delivered in 33 patients. Thirty-two patients received hyperfractionated accelerated radiation therapy with a median dose of 64.6Gy (1.7Gy/fr bid). Conventional external irradiation with a median dose of 66Gy (2Gy/fr) was delivered to 18 patients. An intracavitary brachy-boost of 4.5-12Gy was delivered to 40 patients. Two patients were excluded from the analysis due to treatment refusal. For the patients with tumor stages I-IVB, the 5-year disease-free and overall survival rates were 61% and 55%, respectively. The 5-year local, regional, and distant relapse-free survival rates were 70%, 92% and 77%, respectively. The most frequent late side effects were xerostomia (98%), otitis (70%) and hearing deterioration (64%). Our data suggest that optimization of the treatment outcomes in NPC patients requires implementation of new therapeutic strategies. [ABSTRACT FROM AUTHOR]

Purpose. The use of radiation therapy (RT) together with improvement in the surgical treatment of rectal cancer improves survival and reduces the risk for local recurrences. Despite these benefits, the adverse effects of radiation therapy limit its use. The aim of this review was to present a comprehensive overview of published studies on late adverse effects related to the RT for rectal cancer. Methods. Meta-analyses, reviews, randomised clinical trials, cohort studies and case-control studies on late adverse effects, due to pre- or postoperative radiation therapy and chemo-radiotherapy for rectal cancer, were systematically searched. Most information was obtained from the randomised trials, especially those comparing preoperative short-course 5×5 Gy radiation therapy with surgery alone. Results. The late adverse effects due to RT were bowel obstructions; bowel dysfunction presented as faecal incontinence to gas, loose or solid stools, evacuation problems or urgency; and sexual dysfunction. However, fewer late adverse effects were reported in recent studies, which generally used smaller irradiated volumes and better irradiation techniques; although, one study revealed an increased risk for secondary cancers in irradiated patients. Conclusions. These results stress the importance of careful patient selection for RT for rectal cancer. Improvements in the radiation technique should further be developed and the long-term follow-up of the randomised trials is the most important source of information on late adverse effects and should therefore be continued. [ABSTRACT FROM AUTHOR]

Chemotherapy dosing only based on body surface area (BSA) results in marked pharmacokinetic and toxicity variations, which may result in an inferior outcome for some patients. A toxicity-based dosing schedule for individually tailored treatment with granulocyte colony-stimulating factor (G-CSF) supported 5-fluorouracil (F), epirubicin (E) and cyclophosphamide (C) (dFEC) was developed and studied in patients with metastatic breast cancer with the purpose to determine its efficiency and toxicity. Twenty-six women, median age 48 years, were included and the individual E and C doses were tailored stepwise based on the recorded hematological toxicity. Twenty-one patients (81%; 95% confidence interval (CI), 66% to 96%) had an objective response, including six complete responses (23%; CI, 7%–39%). At median follow-up of 113 months, the median time to progression and median overall survival were 14 and 36 months, respectively. The delivered dose intensity was high but varied substantially between patients (ranges F 126–202, E 14.4–36.0, C 160–510 mg/m2/w). The dominating grade III/IV toxicity was nausea (12% of patients) and febrile neutropenia (31% of patients). The tailored and dose-escalated FEC was highly active and feasible in metastatic breast cancer and may provide a pragmatic way of overcoming the shortcomings of standard BSA-based dosing. [ABSTRACT FROM AUTHOR]

We aimed to identify pretreatment and treatment factors that may influence the outcome of Ewing's sarcoma family tumors of bone and enable customized therapy for future studies with a retrospective analysis of 579 patients with non-metastatic Ewing's sarcoma treated with combined adjuvant or neoadjuvant chemotherapy at a single institution between 1972 and 1998. We evaluated the prognostic significance of gender, age, site and volume of tumor, serum level of LDH, type of local treatment, type of chemotherapy and histologic response to preoperative treatment. The 5- and 10-year disease-free survival rates were 56.9% and 49.2% respectively. Multivariate analyses showed that all the evaluated factors, with exclusion of the tumor site, were significantly correlated with the 5-year disease-free survival. We concluded that the outcome of non-metastatic ESF of bone tumors is influenced by many clinical and treatment-correlated variables. In order to gain the greatest benefit from treatment, while reducing the morbidity, appropriate therapeutic strategies for different risk groups of patients should be selected. Criteria to stratify patients according to the risk of local or systemic relapse should not be based on a single prognostic factor, but should include all the variables that showed prognostic significance. [ABSTRACT FROM AUTHOR]

A systematic review of radiation therapy trials in several tumour types was performed by The Swedish Council of Technology Assessment in Health Care (SBU). The procedures for evaluation of the scientific literature are described separately (Acta Oncol 2003; 42: 357-365). This synthesis of the literature on radiation therapy for head and neck cancer is based on data from 39 randomized trials and 1 meta-analysis. In total, 40 scientific articles are included, involving 20 893 patients. The results were compared with those of a similar overview from 1996 including 79 174 patients. The conclusions reached can be summarized as follows: General, non-nasopharynx Substantial evidence indicates that the tumour effect of radiotherapy can be increased by the concomitant administration of chemotherapeutic agents, particularly cisplatin and 5-fluorouracil. There is moderate evidence of a survival benefit of radiation combined with concomitant chemotherapy compared to radiation alone. However, the results are equivocal. There is substantial evidence in published studies for an increased frequency of severe acute side effects as a result of concomitant chemotherapy and radiotherapy. There are very few studies that allow any estimates of the risk for serious late side effects. There is a weak indication of an increased risk for serious fibrosis. Comment: The general quality of studies and the lack of information on serious side effects indicate a need for large, well-designed clinical studies with a reasonable follow-up. Larynx preservation studies There is strong evidence that larynx preservation is possible in 50% of the patients surviving for 5 years with hypopharyngeal cancers when treated with neoadjuvant chemotherapy and radical radiotherapy. There is a non-significant trend for the overall survival being lower in non-surgically treated patients than in those treated with primary surgery and postoperative radiotherapy. Nasopharynx There is moderate evidence that patients with nasopharyngeal carcinomas of the endemic type benefit from therapy with a combination of chemotherapy and radical radiotherapy. However, the results from the reported studies are equivocal. There is some indication that the acute side effects of radiation are more severe in the concomitant setting than in the neoadjuvant. Comment: There are no data on serious late toxicity. Dose, fractionation schedules There is some evidence that certain schedules of altered fractionation improve tumour control without increasing severe late side effects. There is some evidence that nervous tissues are more susceptible to damage by altered fractionation. Solid data shows that altered fractionation increases acute side effects. There is moderate evidence that accelerated hyperfractionation may reduce the frequency of serious late side effects while retaining a similar tumour effect as conventional radiotherapy. Hypoxic cell sensitizers Most reported trials reject the usefulness of nitroimidazole derivatives for sensitization of hypoxic tumour cells. There is some evidence that patients with tumours in the pharynx and larynx may benefit from sensitization by nimorazole. Prophylactic treatment of side effects There is weak evidence that local antibiotics have a clinically significant effect in preventing acute radiotherapy side effects. There is insufficient evidence that radioprotective agents offer clinically significant protection of parotid glands (one study in two publications). There is insufficient evidence that radioprotective agents do not spare tumour tissue. Since the previous report no randomized studies comparing the effectiveness of external beam radiotherapy and brachytherapy have been performed. Both methods are well established and have independently proved to be effective in the treatment of certain head and neck cancers. No conclusion can be drawn regarding their relative effectiveness. Since the previous report no data to guide the use of intraoperative radiotherapy have been identified. [ABSTRACT FROM AUTHOR]