Multimodality Treatment Of Patients Research Articles

Rektumkarzinom: Aktueller Stand der multimodalen Therapie – wann und wie?

Preoperative 5-fluorouracil-based radiochemotherapy (RCT) followed by quality assessed total mesorectal excision (TME surgery) are the two most important elements of multimodal treatment for patients with locally advanced rectal cancer (UICC stages II and III). The optimum sequence of these neoadjuvant modalities complemented by adjuvant (postoperative) chemotherapy, has been addressed in several randomised trials. Especially within the trials of the German Rectal Cancer Study Group (GRCSG), preoperative RCT has been shown to be superior to postoperative treatment for a variety of endpoints (pathologically confirmed complete tumour remission (pCR), RCT-induced tumour regression, R0 resection rates (including circumferential resection margins) and long-term locoregional control). This neoadjuvant multimodal strategy has decreased the 5-year and 10-year local recurrence rates below 10%, and the development of distant metastases (e.g., 35% to 45% liver metastases) remains the predominant reason for failure. Furthermore, approximately 25% of patients do not receive adjuvant chemotherapy, mainly due to surgical complications, patients' refusal or the investigator's discretion. Thus, today, integrating more effective systemic therapy into (preoperative) multimodal regimens is the most accepted challenge! But from the clinical point of view this demand is also a dilemma. The question to be addressed is how and when to apply intensified systemic therapy with adequate dosage and intensity as well as acceptable treatment-associated toxicity. The increase of therapeutic options requires valid predictive biomarkers that may help to stratify patients into regimens associated with low toxicity (5-FU monotherapy alone) or into more intensified treatment for better long-term outcome. In summary, the use of biomarkers for individualised risk-adapted treatment is one of the most promising areas of clinical investigations, not only in rectal cancer. The assessment of individual tumour response, toxicity, and prognosis during multimodal treatment of rectal cancer as a model of a very common solid tumour offers radiooncologists, surgeons, pathologists, gastroenterologists as well as oncologists immense insights into the under-standing of tumour biology.

The impact of capecitabine and oxaliplatin in the preoperative multimodality treatment in patients with carcinoma of the rectum: NSABP R-04.

3503 Background: The optimal chemotherapy regimen to be given concurrently with preop radiation therapy (RT) in patients with resectable adenocarcinoma of the rectum is unknown. NSABP R-04 compared the efficacy of 4 chemotherapy regimens administered concomitantly with preop RT. Methods: Patients with clinical stage II or III rectal cancer undergoing preop RT (4,500cGy in 25 fractions over 5 wk + boost of 540cGy-1080cGy in 3-6 daily fractions) were randomly assigned to one of the following chemotherapy regimens: continuous IV infusion (CVI) 5-FU (225mg/m2 5 days/wk), with or without IV oxaliplatin (OX) (50mg/m2 /wk x 5); oral capecitabine (CAPE) (825 mg/m2 BID 5 days/wk), with or without OX (50mg/m2/wk x 5). Prior to random assignment the surgeon indicated if the patient was eligible for sphincter-saving surgery (SSS) based on clinical staging. The endpoints were complete pathologic response (pCR), SSS, and surgical downstaging (SD, conversion to SSS). Results: From July 2004 to August 2010, 1,608 patients were randomly assigned. No significant differences in the rates of pCR, SSS, or SD were identified between the 5-FU and CAPE regimens or between the regimens, with and without OX (Table). Patients treated with OX experienced significantly more grade 3/4 diarrhea. Conclusions: Administration of capecitabine with preop RT achieved similar rates of pCR, SSS, and SD compared to CVI 5-FU. The addition of oxaliplatin did not improve preliminary outcomes but added significant toxicity. The definitive analysis of local tumor control will be performed in fall 2013. Funded by NCI PHS grants U10-CA-37377, U10-CA-69974, U10-CA-12027, U10-CA-69651, and U10-CA-25224 with support from sanofi-aventis US Inc. and Hoffmann La-Roche. Endpoint 5-FU (± OX) CAPE (± OX) P value pCR 135/719 = 18.8% 157/707 = 22.2% 0.12 SSS 445/727 = 61.2% 445/710 = 62.7% 0.59 SD 39/188 = 20.7% 43/187 = 23.0% 0.62 Grade 3/4 diarrhea 70/625 = 11.2% 68/628 = 10.8% 0.86 Endpoint (FU or CAPE) No OX (FU or CAPE) + OX P value pCR 111/580 = 19.1% 121/578 = 20.9% 0.46 SSS 370/582 = 63.6% 353/584 = 60.4% 0.28 SD 35/152 = 23.0% 29/151 = 19.2% 0.48 Grade 3/4 diarrhea 41/622 = 6.6% 97/631 = 15.4% < 0.0001

Surgical density and its effect on esophageal cancer (EC) and gastric (GC) mortality.

16 Background: Surgical resection plays an integral role in the multimodality treatment of patients with EC or GC. The distribution of thoracic and general surgeons at the county level varies widely across the US. The impact of the allocation of these surgeons on cancer outcomes is unclear. Our aims were to 1) examine the effect of surgeon density on EC or GC mortality, 2) compare the relative roles of thoracic and general surgeons on EC and GC outcomes and 3) determine other county characteristics associated with cancer mortality. Methods: Using county-level data from the Area Resources File, U.S. Census and National Cancer Institute, we constructed regression models to explore the effect of thoracic and general surgeon density on EC and GC mortality, respectively. Multivariate analyses controlled for incidence rate, county demographics (population aged 65+, proportion eligible for Medicare, education attainment, metropolitan vs. rural), socioeconomic factors (median household income) and healthcare resources (number of general practitioners, number of hospital beds). Results: In total, 332 and 402 counties were identified for EC and GC, respectively: mean EC/GC incidence = 5.29/6.83; mean EC/GC mortality=4.70/3.92; 91% were metropolitan and 9% were rural; mean thoracic and general surgeon densities were 10 and 63 per 100,000 people, respectively. When compared to counties with no thoracic surgeons, those with at least 1 thoracic surgeon had reduced EC mortality (beta coefficient -0.031). For GC, counties with 1 or more general surgeons also had decreased number of deaths (beta coefficient -0.095) when compared with those without any surgeons. While increasing the density of surgeons beyond 10 only yielded minimal improvements in EC mortality, it resulted in significant further reductions in GC mortality. Other county characteristics, such as increased number of hospital beds and higher median household income, were correlated with improved outcomes. Conclusions: Mortality from GC appears to be more susceptible to the benefits of increased surgeon density. For EC, a strategic policy of allocating health resources and distributing the workforce across counties will be best able to optimize outcomes at the population-level. No significant financial relationships to disclose.

Impact of PET‐CT on Primary Staging and Response Control on Multimodal Treatment of Esophageal Cancer

The predictive value of positron emission tomography-computed tomography (PET-CT) in primary staging and response control in patients with esophageal carcinoma (EC) is under discussion. In the present study initial staging and metabolic response of PET-CT was correlated with tumor regression and survival in patients with multimodal treatment of EC. The authors conducted a retrospective analysis on a prospective database for 83 patients with EC (42 squamous cell, 39 adenocarcinoma, 2 anaplastic carcinoma) undergoing PET-CT for primary staging. Twenty-four of the patients underwent primary esophagectomy, 9 had palliative treatment, and 50 neoadjuvant radiochemotherapy (cisplatin, 5-fluorouracil; 50.4 Gy). The PET-CT study was repeated 6 weeks after induction of chemotherapy and compared with endoscopic ultrasound (EUS). For response control, the metabolic response (tumor standardized uptake value [SUV] reduction) was correlated with histopathologic (ypT0-4) and histomorphologic response (tumor regression) and survival. At primary staging 81 of 83 EC (97.5%) showed an increased SUV uptake correlating with the EUS tumor stage. Suspicious lymph nodes were detected in 51 (61.4%) patients by PET-CT and 66 (79.5%) were detected by EUS. Fifteen patients had additional findings on PET-CT examination leading to a change in therapy in 9 patients (10.3%). Of 50 patients receiving a second PET-CT study, a SUV reduction >50% correlated with major histomorphologic response (tumor regression grade 4, <10% vital tumor cells) and histopathologic response (ypT0 ypN0). Furthermore, these patients showed a significantly increased survival (33.1 ± 3.5 months) compared to non-responders (21.7 ± 3.3 months; p = 0.02) and patients after primary surgery (29 ± 3.2 months; p = 0.05). The present study shows that PET-CT is a valuable tool for primary staging and response control in multimodal treatment of patients with EC.

Oral Nutritional Supplements Containing (n-3) Polyunsaturated Fatty Acids Affect the Nutritional Status of Patients with Stage III Non-Small Cell Lung Cancer during Multimodality Treatment1–3

Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), (n-3) fatty acids from fish oil, have immune-modulating effects and may improve nutritional status in cancer. The objective of this study was to investigate the effects of an oral nutritional supplement containing (n-3) fatty acids on nutritional status and inflammatory markers in patients with non-small cell lung cancer (NSCLC) undergoing multimodality treatment. In a double-blind experiment, 40 patients with stage III NSCLC were randomly assigned to receive 2 cans/d of a protein- and energy-dense oral nutritional supplement containing (n-3) fatty acids (2.0 g EPA + 0.9 g DHA/d) or an isocaloric control supplement. EPA in plasma phospholipids, energy intake, resting energy expenditure (REE), body weight, fat free mass (FFM), mid-upper arm circumference (MUAC), and inflammatory markers were assessed. Effects of intervention were analyzed by generalized estimating equations and expressed as regression coefficients (B). The intervention group (I) had a better weight maintenance than the control (C) group after 2 and 4 wk (B = 1.3 and 1.7 kg, respectively; P < 0.05), a better FFM maintenance after 3 and 5 wk (B = 1.5 and 1.9 kg, respectively; P < 0.05), a reduced REE (B = −16.7% of predicted; P = 0.01) after 3 wk, and a trend for a greater MUAC (B = 9.1; P = 0.06) and lower interleukin-6 production (B = −27.9; P = 0.08) after 5 wk. After 4 wk, the I group had a higher energy and protein intake than the C group (B = 2456 kJ/24 h, P = 0.03 and B = 25.0 g, P = 0.01, respectively). In conclusion, a protein- and energy-dense oral nutritional supplement containing (n-3) fatty acids beneficially affects nutritional status during multimodality treatment in patients with NSCLC.

Multimodal treatment of patients with minor salivary gland cancer in the case of recurrent disease

Our aim in this study was to identify prognostic factors and the optimal therapeutic management in patients with minor salivary gland carcinomas. Overall and disease-free survival and overall survival after recurrence in patients with adenoidcystic carcinoma (n = 25), mucoepidermoid carcinoma (n = 8), adenocarcinoma (n = 5), carcinoma ex pleomorphic adenoma (n = 4), and others (n = 5) were correlated to clinical data. Overall survival correlated to treatment modality (p = .039) and T classification (p = .003), whereas prolonged disease-free interval correlated to treatment (p < .001) and T classification (p = .009). Overall survival after recurrence correlated to treatment of recurrence (p = .006) and initial T classification (p = .02). Multivariate analysis showed that overall survival after recurrence correlated to treatment of recurrence (p = .019) and initial T classification (p = 0.019). T classification was a prognostic factor for overall survival (p = .002) and disease-free interval (p = .002). The initial tumor classification is a clinical predictor for patients' overall and disease-free survival and overall survival after recurrence. Multimodal treatment significantly improves patients' overall survival.

Zytoreduktive Chirurgie und hypertherme intrathorakale Chemotherapieperfusion

Recently cytoreductive surgery of primary and secondary pleural tumors has been combined with hyperthermic intrathoracic chemotherapy perfusion (HITHOC) for better local tumor control. In comparison to simple instillation of chemotherapeutic agents into the pleural cavity, the combination of surgical resection of pleural tumors and simultaneous HITHOC seems to be a more effective treatment. Intra-operative perfusion allows an improved distribution of the drug in the pleural space and a higher local concentration of the chemotherapeutic agents in contrast to systemic chemotherapy. Additional advantages of HITHOC are a better response to chemotherapeutic agents and synergistic antineoplastic effects. A prerequisite for safe application of HITHOC is compliance with safety regulations. Due to the reduction in morbidity and mortality this new concept is a valuable alternative for selected patients who do not undergo radical resection (e.g. extrapleural pneumonectomy). HITHOC is an additional therapeutic option in the multimodal treatment of patients with primary or secondary tumors of the pleura.

Endolumbar nootropic-ozone therapy in multimodality treatment of patients with a complicated spinal injury at its acute period

Surgical treatment of 39 patients with complicated injuries of the vertebral column was analysed. In order to increase the efficacy of treatment in the main group of patients (25 observations), an endolumbar injection of Pyracetam and ozone during the postoperative period was used. The obtained data showed that after 2-3 endolumbar injections of Pyracetam and ozone within the postoperative period 16 (64.0 %) patients revealed development of sensitivity below the level of injured spinal cord segments and movements in the distal parts of their lower extremities. In 6 (24.0 %) patients neurological symptoms improved after 5-6 injections. In patients of the control group (14 observations), who did not undergo the above nootropic-ozone therapy, moderately positive neurological symptoms were found out only in 35.7 % of cases. In 64.3 % of cases their neurological symptoms remained on the same level despite decompressive-stabilizing operations made.

18F]-Fluorodeoxyglucose-Positron Emission Tomography for the Assessment of Histopathologic Response and Prognosis After Completion of Neoadjuvant Chemoradiation in Esophageal Cancer

To evaluate the potential of [(18)F]-fluorodeoxyglucose-positron emission tomography (FDG-PET) after the completion of neoadjuvant chemoradiation for the assessment of histopathologic response and prognosis in the multimodality treatment of patients with esophageal cancer. Combined chemoradiation with and without surgery are widely accepted treatment options for patients with locally advanced esophageal cancer. Evidence suggests that patients with response to chemoradiation have no additional benefit from surgery compared with definitive chemoradiation. However, there is still a great lack in noninvasive markers for response assessment in patients with esophageal cancer undergoing multimodality treatment. Interestingly, recent studies imply that FDG-PET significantly correlates with histopathologic response and survival in patients with esophageal cancer undergoing neoadjuvant chemotherapy followed by surgical resection. Study patients were recruited from a prospective clinical observation trial on neoadjuvant chemoradiation for esophageal cancer between 1997 and 2006. The study included 119 (98 men, 21 women; median age, 59.4 years; squamous cell cancer: 66; adenocarcinoma: 53) patients with locally advanced esophageal cancer (cT2- 4, N(x), M(0)). All patients received neoadjuvant chemoradiation (cisplatin, 5-FU, 36 Gy) and subsequently underwent transthoracic en bloc esophagectomy. Histomorphologic regression was defined as major histopathologic response when resected specimens contained less than 10% vital residual tumor cells (major response: 47 patients [39.5%]; minor response: 72 patients [60.5%]). FDG-PET was performed before and 2 to 3 weeks after the end of chemoradiation with assessment of the intratumoral FDG-uptake (pretreatment standardized uptake value; post-treatment standardized uptake value; percentage change). These variables were correlated with histopathologic response and survival. Major histomorphologic response was confirmed as an important prognostic factor (P = 0.005; log-rank test). Neoadjuvant chemoradiation led to a significant reduction of intratumoral FDG-uptake (P = 0.0001). A nonsignificant association was seen between major responders and FDG-PET results (P = 0.056). However, the receiver operating characteristic analysis could not identify a standardized uptake value threshold with a relevant predictive value for histomorphologic response. No significant association between metabolic imaging and prognosis was found. FDG-PET seems not to be an imaging system that effectively characterizes the groups of major and minor response as well as survival in patients with esophageal cancer after multimodality treatment.

Impact of yoga on chronic pain—A review

Purpose Mind–Body therapies are considered as adjunctive treatments to help ameliorate or at least cope with chronic pain conditions. Despite a lack of scientific acceptance, these approaches are of interest to patients which widely use relaxation techniques, biofeedback, imagery, hypnosis, etc. We intended to analyze the scientific literature with respect to the impact of yoga on chronic pain conditions. Methods In January 2009 we searched the databases Medline, Pubmed and CAMbase. The search terms were >yoga pain Results We found 15 studies which addressed the impact of yoga on chronic pain conditions. The studies enrolled patients with chronic low back pain ( n =6), headache/migraine ( n =2), various other chronic pain conditions ( n =6), and one experimental study with healthy individuals. Fourteen studies addressed pain perception or disability, 6 mood states (anxiety/depression) and distress, and one study health-related quality of life. Nine studies were randomized, 2 controlled, and 3 had a single arm design; one study was an experimental study with yoga trained and non-trained individuals. The number of patients in the randomized or controlled studies ranged from 15 to 101. The randomized and controlled studies described positive effects in terms of decreased pain frequency and intensity, decreased anxiety/depression, and improvement of fatigue- and health-related quality of life. Conclusions There is reasonable evidence that yoga practices may have positive effects on pain perception and mood states. The overall positive findings in the identified studies indicate that yoga may enhance patients’ self-efficacy, inner balance, adjustment and coping abilities. Nevertheless, there are several research questions, which have to be addressed in future studies, i.e., adequate control interventions; patients’ positive expectations; patients’ ability and will to change behavior, etc. Several of the unspecific effects of distinct mind–body therapies are nevertheless critical aspects (i.e., expectancy, sense of control, mindfulness, etc.) which cannot be ignored as they contribute to the intended treatment effect. Mind–body interventions such as yoga may become important adjunctive interventions in the multi-modal treatment of patients with chronic pain conditions as they foster self-control and self-management.

Inflammatory breast carcinoma as a model of accelerated self-metastatic expansion by intravascular growth

Inflammatory breast carcinoma as a model of accelerated self-metastatic expansion by intravascular growth

Evaluation of response in the multimodality treatment of esophageal cancer by [18F]-fluorodeoxyglucose-positron emission tomography: A systematic review and meta-analysis

e15520 Background: Neoadjuvant therapy followed by surgery is frequently applied to improve the prognosis of patients with esophageal cancer. However, only a major histopathological response will provide a survival benefit. On the other hand, evidence suggests that patients with response to chemoradiation have no additional benefit from surgery compared with definitive chemoradiation. Consequently, effective methods for early and late response assessment are required in order to perform these different individualised, response-guided treatment concepts. The value of [18F]-fluorodeoxyglucose-positron emission tomography (FDG-PET) for this diagnostic purpose is still under debate. This systematic review and meta-analysis aims to evaluate the potential of FDG-PETfor the assessment of response in the multimodality treatment of patients with esophageal cancer. Methods: A systematic literature search of studies published between 1990 and September 2008 was performed. The meta-analysis estimated the pooled sensitivity and specificity of histopathological response assessment by FDG-PET using a random effect model. Results: Thirty relevant studies with 1151 patients (865 adenocarcinoma, 493 squamous cell cancer) were identified and included in the systematic review. Mainly neoadjuvant chemoradiation (22 studies) was performed. FDG-PET was conducted mostly before and after neoadjuvant therapy (21 studies) and second most (6 studies) the subsequent FDG-PET was scheduled 7–14 days after the initiation of preoperative therapy. Sixteen studies were included in the meta-analysis. For metabolic response assessment 7–14 days after the initiation of therapy, including 254 patients (with 5 studies from one center), the pooled sensitivity was 85.5% (95% CI: 75.5%-92.8%) and specificity 76.1% (95% CI: 69.3%-82.0%). For late response assessment, including 446 patients, the pooled sensitivity was 77.1% (95% CI: 72.8%- 81.0%) and specificity 59.0% (95% CI: 55.3%-62.7%). Conclusions: For early response assessment FDP-PET seems to be useful in the multimodality treatment of esophageal cancer. In contrast, this study suggests FDG-PET invaluable for late response assessment. No significant financial relationships to disclose.

Surgical Resection Is Justified in Non-Small Cell Lung Cancer Patients with Node Negative T4 Satellite Lesions

The management of non-small cell lung cancer (NSCLC) depends on the stage, with a satellite nodule in the same lobe being classified as T4 stage IIIB even in node negative patients. Controversy exists as to the optimal management of these patients. Our objectives were to evaluate the outcomes in surgically resected patients with a T4 satellite lesion and to analyze the prognostic factors associated with outcome. Patients who underwent resection for T4 (satellite nodule) N0-2M0 were identified. Patients with pure bronchoalveolar carcinoma were excluded. The primary endpoint studied was overall survival. Multiple covariates were analyzed for association with survival and recurrence. A total of 51 T4 N0-2 patients (men 22, women 29; median age 71 years [48 to 87]) underwent resection over a 7-year period. At a median follow-up of 26.4 months the estimated 5-year overall survival was 26% (95% confidence interval [CI] 14% to 50%; median survival 25.2 months). The estimated 5-year overall survival for T4 N0 patients was 40% (95% CI 23% to 68%; median survival 34.8 months). Size of the primary tumor, histology, and nodal status were significantly associated with overall survival; size and nodal status were significantly associated with disease-free survival. Our results indicate that T4 (satellite nodule) N0 patients experienced excellent survival after surgical resection. These data support surgical resection in node negative patients. Size, histology, and nodal status were important prognostic variables associated with outcome. Consideration should be given to multimodality treatment in patients with adverse prognostic features. Further larger multiinstitutional studies are required to validate these findings.

Surgical Treatment and Prognosis of Primitive Neuroectodermal Tumors of the Thorax

Primitive neuroectodermal tumors (PNETs) are rare, rapidly progressive, small- round cell tumors with a poor prognosis despite multimodal therapy, including surgery and chemoradiotherapy. The treatment of choice was unknown since no clinical series with surgical therapy had been reported. We evaluated the impact of multimodal treatment in patients with PNETs located in the thoracic region. Between 1998 and 2006, 25 patients with PNETs in the thoracic region were treated in 3 tertiary-care hospitals. The patients consisted of 15 males and 10 females with a mean age of 27.2 years (range, 6-60). The tumor was in the chest wall in 20 (involving the costovertebral junction in 9), the lung in four, and the heart in one patient. Twelve patients received neoadjuvant chemotherapy (54.5%), and 22 of 25 patients underwent surgery. In patients who received neoadjuvant treatment, the mean regression rate was 65.4% (range, 30-100%). Eighteen (82%) patients underwent chest wall resection, while 7 (32%) had vertebral resections, and the remaining 4 (16%) had pulmonary resections. A complete resection was possible in 18 of 22 patients (82%). Patients with incomplete and complete resections had 25% and 56% 5-year survival rates, respectively (p = 0.13). The progression-free 3-year survival rate was 36% and the median survival time was 13 months. The complete resection rate was significantly higher in patients receiving neoadjuvant therapy (p = 0.027). The 5-year survival rate of the patients with or without neoadjuvant therapy was 77% and 37%, respectively (p = 0.22) although it prolonged the disease-free survival (p = 0.01). The 5-year survival rate of patients without costovertebral junction involvement was 66%, whereas patients with PNETs involving the costovertebral junction had a 21% 3-year survival. The difference was statistically significant (p = 0.01). The 5-year progression-free survival rate of patients without costovertebral junction involvement was 58%, whereas patients with PNETs involving the costovertebral junction had a 14% 1-year progression-free survival (p = 0.004). PNET is an aggressive malignancy that often requires multimodal therapy. Induction chemotherapy leads to a greater complete resection rate and better disease-free survival, while involvement of the costovertebral junction indicates a poorer survival.

Circumferential Margin Involvement is the Crucial Prognostic Factor after Multimodality Treatment in Patients with Locally Advanced Rectal Carcinoma

Circumferential Margin Involvement is the Crucial Prognostic Factor after Multimodality Treatment in Patients with Locally Advanced Rectal Carcinoma

CLINICAL-BIOMECHANICAL AND PHYSIOLOGICAL RESULTSOF MULTIMODAL CONSERVATIVE TREATMENTOF PATIENTS WITH GRADE II–III IDIOPATHIC SCOLIOSIS

Objective. To analyze the efficacy of multimodal treatment of patients with grade II—III idiopathic scoliosis comprising artificial correction of movements (ACM) by means of functional electric stimulation (FES) of muscles during walking in a correcting brace. Material and Methods. The subjects of examination and treatment were 50 patients with idiopathic scoliosis, among them 20 patients with grade II spinal curvature, and 30 — with grade III. Brace therapy was performed with a functional frame-type brace modified by adding lateral pelottes attached with springs. All patients received 15‑day course of FES during walking in a functional correcting brace. Electric stimulation was applied to trunk muscles of both sides: sacrospinous, intercostal, rhomboidal, trapezius, as well as greatest and medium gluteal muscles at the concave side of the curvature. Results. The study showed that multimodal treatment facilitates significant correction of different types of spinal deformity and normalization of biomechanical and innervation structure of walking. Long-term outcomes were evaluated in 36 patients during a 3‑year follow-up period. With the adherence to a prescribed orthopedic treatment regimen and repeated FES courses each 8—10 months the long-term outcome was good in 29 cases and satisfactory in 8 cases. Conclusion. The effect was achieved by reduction of scoliosis, essential intensification of the activity of symmetric trunk and leg muscles, and improvement of their functioning during walking.

Lack of fludeoxyglucose F 18 uptake in posttreatment positron emission tomography as a significant predictor of survival after subsequent surgery in multimodality treatment for patients with locally advanced esophageal squamous cell carcinoma

Patients with advanced esophageal squamous cell carcinoma receive neoadjuvant chemotherapy or chemoradiotherapy to improve survival, but benefits are observed only in those with histologic response. Positron emission tomography with fludeoxyglucose F 18 (INN fludeoxyglucose [(18)F]) detects accumulation of glucose analog in viable cancer cells. This study investigated the usefulness of positron emission tomography with fludeoxyglucose F 18 in assessment of response of advanced esophageal squamous cell carcinoma to neoadjuvant treatment to establish new criteria to predict postoperative long-term survival. Fifty patients with locally advanced esophageal squamous cell carcinoma who received neoadjuvant therapy (chemotherapy 35, chemoradiotherapy 15) underwent positron emission tomography with fludeoxyglucose F 18 before surgical resection in evaluation of posttreatment maximum standardized uptake value, residual tumor size (maximum square area of longitudinal axis), histologic response, and postoperative survival. After treatment, uptake was not noted in 21 patients (posttreatment maximum standardized uptake value < 2.5, negative) but was detected in 29 (> or = 2.5, positive). Residual tumor size ranged from 0 to 54.0 mm(2) for negative results and 55.0 to 676.0 mm(2) for positive, clearly distinguishing histologic major response from nonresponse. The negative group demonstrated significantly higher 5-year cause-specific survival (67.7%) and lower hematogenous recurrence (4.8%) than the 36.5% and 37.0% values in the positive group, (P < .0042 and P = .0083, respectively). Univariate Cox regression analyses identified posttreatment maximum standardized uptake value (cutoff 2.5) as the only preoperative prognostic factor (P = .0071). Posttreatment positron emission tomography with fludeoxyglucose F 18 reliably predicted histologic response and postoperative survival in advanced esophageal squamous cell carcinoma. This tool could potentially be used to tailor optimal treatment according to individual responses.

Limitations of positron emission tomography in predicting histopathologic response or prognosis following neoadjuvant chemoradiation for esophageal cancer

4529 Background: Neoadjuvant chemoradiation is frequently applied to improve the prognosis of patients with advanced esophageal cancer. However, only a major histopathological response will provide a survival benefit. Recent studies suggest that [18F]-fluorodeoxyglucose-positron emission tomography during neoadjuvant chemotherapy significantly correlates with histopathological response and survival in patients with resected esophageal adenocarcinoma. Aim of this study was to evaluate the predictive and prognostic potential of FDG-PET in the multimodality treatment of patients with esophageal cancer. Methods: Study patients were recruited from a prospective clinical observation trial on neoadjuvant chemoradiation for esophageal cancer between 1997 and 2006. 133 patients with advanced esophageal cancer (uT2–4, Nx, M0) were included. All patients received neoadjuvant chemoradiation (cisplatin, 5-FU, 36 Gy) and underwent transthoracic en bloc esophagectomy. Histomorphologic regression was defined as major histopathological response when resected specimens contained less than 10 % vital residual tumor cells (major response: 52 patients; minor response: 81 patients). FDG-PET was performed before and 3–4 weeks after the end of chemoradiation with assessment of the intratumoral FDG-uptake [pre-treatment standardized uptake value (SUV1); post-treatment SUV(SUV2); percentage change (SUVΔ%)]. These variables were correlated with histopathological response and survival. Results: Neoadjuvant chemoradiation led to a significant reduction of intratumoral FDG-uptake (p<0.0001). No significant correlations between SUV1 or SUV2 and histopathological response or prognosis were found. Also, the SUVΔ% did not show any impact: SUVΔ% major response: SUVΔ% minor response=69%/57%. A SUV threshold with predictive or prognostic value was not identified. Histomorphological tumor regression was confirmed as an important prognostic factor (p<0.05). Conclusions: Our study does not support recent reports that the metabolic response by FDG-PET is associated with histomorphological response or survival in patients with esophageal cancer following neoadjuvant therapy and esophagectomy. No significant financial relationships to disclose.

Circumferential Margin Involvement Is the Crucial Prognostic Factor after Multimodality Treatment in Patients with Locally Advanced Rectal Carcinoma

After preoperative (radio)chemotherapy, histologic determinants for prognostication have changed. It is unclear which variables, including assessment of tumor regression, are the best indicators for local recurrence and survival. A series of 201 patients with locally advanced rectal cancer (cT3/T4, M0) presenting with an involved or at least threatened circumferential margin (CRM) on preoperative imaging (<2 mm) were evaluated using standard histopathologic variables and four different histologic regression systems. All patients received neoadjuvant radiochemotherapy or radiotherapy. The prognostic value of all factors was tested with univariate survival analysis of time to local recurrence and overall survival. Local recurrence occurred in only 8% of the patients with a free CRM compared with 43% in case of CRM involvement (P < 0.0001). None of the four regression systems were associated with prognosis, not even when corrected for CRM status. However, we did observe a higher degree of tumor regression after radiochemotherapy compared with radiotherapy (P < 0.001). Absence of tumor regression was associated with increasing invasion depth and a positive CRM (P = 0.02 and 0.03, respectively). Assessment of CRM involvement is the most important pathologic variable after radiochemotherapy. Although tumor regression increases the chance on a free CRM, in cases with positive resection margins prognosis is poor irrespective of the degree of therapy-induced regression.

Adjuvant multimodality treatment in patients with high-risk prostate cancer following radical prostatectomy: Results of a prospective clinical phase-II trial

15557 Background: High risk prostate cancer (PCA) is associated with a high frequency of PSA relapse. Even with adjuvant androgen deprivation therapy about 50% of patients experience systemic recurrences within 5 years. Docetaxel has demonstrated significant activity in men with metastatic androgen independent PCA, zoledronic acid has been shown to significantly inhibit the development of osseous metastases. It was the aim of the current prospective clinical phase-II trial to evaluate safety and clinical efficacy of early multimodality treatment in high risk PCA after radical prostatectomy (RPE). Methods: Between 3/2004 and 12/2005 25 patients with high risk PCA following RPE were recruited. High risk PCA was defined by a risk of biochemical progression &gt; 70% according to the postoperative Kattan nomograms. Adjuvant therapy consisted of androgen deprivation with LHRH analogues for 12 months, zoledronic acid at 4mg every 3 months and docetaxel at 75 mg/qm for six consecutive cycles. Adjuvant treatment was initiated 4 to 6 weeks after surgery. Follow-up examination were undertaken every 3 months with PSA serum determinations; in case of PSA increase 2 consecutive measurements at 4 weeks intervals were performed. Time to progression defined the time interval between initiation of therapy and first PSA relapse. Results: The mean follow-up is 20.5 (6–31) months. Adjuvant multimodality treatment was well tolerated in all patients with grade 3/4 hematotoxicity in 3 (12%) and gastrointestinal toxicity in 5 (16%) patients; 2 (8%) developed significant oncolysis with surgical intervention. In none of the patients the dosage of docetaxel or the number of cycles had to be reduced. Currently, 4 (16%) patients have developed PSA relapse with 2 exhibiting osseous metastases and 2 having died. Median time to progression was 14.5 (10–16) months. Conclusions: The clinical efficacy appears to be lower than expected with a 16% progression rate and a 8% mortality rate after only 20 months of follow-up. Adjuvant multimodality treatment of high risk PCA after RPE can be applied without significant treatment-associated side effects. Currently ongoing clinical phase-III trials have to further validate the concept of adjuvant chemotherapy. No significant financial relationships to disclose.