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Therapeutic options for the treatment of small cell and non-small cell lung cancer.

Although much of the excitement over pending advances in molecular biology may apply to therapy for non-small cell lung cancer, the practicing oncologist will still be faced with current treatments for the next several years. Little new research in the area of small cell lung cancer was reported, although the issue of consolidative chest irradiation appears to be resolved in favor of its use. To date, more chemotherapy is not better for small cell lung cancer. Treatment of non-small cell lung cancer remains difficult, although there are clear indications that chemotherapy with radiation is superior to radiation alone. Chemotherapy for non-small cell lung cancer advanced only marginally; several promising agents are just now coming into phase III trial in combination with established agents. Neoadjuvant therapy remains a confused arena, with a potpourri of different regimens and approaches combined with a nonstandardized approach to staging. Therapy for malignant pleural effusions also remains difficult, with even the best agent demonstrating a 30% to 40% treatment failure rate.

Carcinoma, Non-Small-Cell Lung↗

Results of a planned interim toxicity analysis with trimodality therapy, including carboplatin AUC = 4, paclitaxel, 5-fluorouracil, amifostine, and radiation for locally advanced esophageal cancer: preliminary analyses and treatment recommendations from the North Central Cancer Treatment Group.

PURPOSE: An aggressive trimodality approach from the Minnie Pearl Cancer Research Network [carboplatin AUC = 6, days 1 and 22; 5-fluorouracil 225 mg/m2 continuous infusion, days 1-42, paclitaxel 200 mg/m2, days 1 and 22; 45 Gy] has resulted in remarkable pathologic response rates but notable toxicity. This trial was designed to mitigate this toxicity by starting with a lower carboplatin dose, AUC = 4, and by adding subcutaneous amifostine. METHODS: This phase II trial included patients with locally advanced, potentially resectable esophageal cancer. All were to receive the above regimen with modifications of carboplatin AUC = 4 and amifostine 500 mg subcutaneously before radiation. All were then to undergo an esophagectomy. A planned interim toxicity analysis after the first 10 patients was to determine whether the carboplatin dose should escalate to AUC = 6. RESULTS: Ten patients were enrolled, and all required dose reductions/omissions during neoadjuvant therapy. One patient died from paclitaxel anaphylaxis. Six patients manifested a complete pathologic response. CONCLUSION: With this regimen, carboplatin AUC = 4 for patients with locally advanced esophageal cancer is appropriate.

Journal Article↗

Gastrointestinal Stromal Tumors Respond to Tyrosine Kinase-targeted Therapy.

Gastrointestinal stromal tumors (GISTs) are rare tumors of the wall of the stomach and small bowel, and also occasionally arise in the mesentery, omentum, or retroperitoneum. The incidence of GIST in the United States is approximately 500 to 750 patients per 100,000 people. GISTs often present late in their clinical course unless they are the cause of gastrointestinal bleeding or perforation. Surgical resection is the standard of care for primary GIST. However, there is a high risk of recurrence in the peritoneum and liver. For metastatic GIST, imatinib mesylate is the standard of care. Two phase III studies presented in 2003 in abstract form show slightly different results. In the US study, 400 mg/d was found to be equivalent to 800 mg/d with respect to response, progression-free survival, and overall survival at 12 months. In the European/Australasian study, the response rate was the same with either dosage, but progression-free survival was better with 800 mg/d compared with 400 mg/d. Overall survival data for the latter study were too immature for analysis as of May 2003. Adjuvant or neoadjuvant therapy with imatinib is the topic of at least three studies through the American College of Surgeons Oncology Group and Radiation Therapy Oncology Group and the American College of Radiology Imaging Network. Every effort to enroll eligible patients on these studies should be made. New treatments for metastatic disease under investigation include a tyrosine kinase inhibitor with an expanded panel of targets compared with imatinib (SU011248), and the addition of a mammalian target of rapamycin (mTOR) inhibitor and the rapamycin derivative RAD001 to imatinib. Given the finding of a specific molecular defect to exploit, GISTs have gone from an orphan disease to a proving ground for tyrosine kinase-targeted therapy.

Journal Article↗

Docetaxel: a review of its use in non-small cell lung cancer.

Docetaxel, a semisynthetic member of the taxoid class of antineoplastic agents, is effective in the treatment of patients with locally advanced and metastatic non-small cell lung cancer (NSCLC). In noncomparative trials in patients with NSCLC, docetaxel 75 or 100 mg/m2 produced objective response rates of 20 to 38% and 14 to 25% as a first-line or second-line monotherapy, respectively. In Japan, docetaxel 60 mg/m2 produced objective response rates of 19 to 25% in previously untreated patients. Docetaxel 100 or 75 mg/m2 produced significantly higher response rates than either vinorelbine or ifosfamide in previously treated patients; patients treated with docetaxel 75 mg/m2 had an improved 1-year survival rate compared with those who received vinorelbine or ifosfamide. Docetaxel monotherapy in chemotherapy-naive patients produced survival rates that are similar to those reported for most platinum-containing standard combinations such as cisplatin plus vinorelbine. Combination of docetaxel with one other antineoplastic resulted in objective response rates of 20 to 54% in chemotherapy-naive patients; triple chemotherapy combinations produced responses in 51 and 60% of patients. Promising results from a few small studies and one large phase II study have also indicated a potential role for docetaxel as neoadjuvant therapy. The main dose-limiting adverse event associated with docetaxel is neutropenia, and fluid retention is common in many patients. The tolerability profile is generally acceptable in the majority of patients, although extra care has to be taken in patients with impaired liver function to minimise the risk of severe or febrile neutropenia. Conclusions. Docetaxel is generally well tolerated by patients receiving treatment for locally advanced and metastatic NSCLC, and produces response and survival rates equivalent to many current standard treatment options. Comparative studies have shown that docetaxel monotherapy provides significant survival benefits over best supportive care or treatment with vinorelbine or ifosfamide. Response and 1-year survival rates with docetaxel monotherapy are particularly encouraging in patients refractory or resistant to cisplatin or carboplatin, for whom treatment options are few. Neoadjuvant docetaxel has produced improved survival compared with local treatment alone. Combinations of docetaxel with other antineoplastic agents have produced relatively high response and 1-year survival rates; however, further comparative studies are required to confirm these benefits. In the meantime, docetaxel is a welcome addition to the options available for patients with advanced NSCLC.

Antineoplastic Agents, Phytogenic↗

Combined modality therapy for stage II and stage III pancreatic carcinoma.

PURPOSE: To study the outcome achieved with three-drug chemotherapy and split-course external-beam radiotherapy as a treatment for unresectable stage II and III pancreatic carcinoma. PATIENTS AND METHODS: Radiotherapy was given in three cycles of 2 Gy/d on days 1 to 5 and 8 to 12 (total dose, 54 Gy) concurrently with fluorouracil (FU) 1,000 mg/m2/d by continuous infusion for 4.5 days, streptozocin (STZ) 300 mg/m2 on days 1, 2, and 3 and cisplatin (P) 100 mg/m2 on day 3 of each every-28-day cycle. Subsequent treatment consisted of leucovorin (LV) 200 mg/m2 and FU 600 to 1,000 mg/m2 every 14 days. RESULTS: The median survival time for the 35 patients was 15 months and 26% of patients were alive at 24 months. Fifteen patients (42.8%) had objective responses to therapy. Six (17%) had a complete response (CR). Three of nine patients with partial responses (PRs) achieved a radiographic CR within the next 3 months. Nine patients underwent attempts at surgical resection: five were resected (median survival time, 31 months; range, 12.8 to 44.7+), two had no residual disease found at complete resection, and three others also had a complete resection. Of four others who could not be resected, three underwent intraoperative radiotherapy and one had occult metastatic disease. Of primary tumors, 91% did not produce either back pain or local gastrointestinal complications for 2 years. The rates of severe side effects were stomatitis 15%, anemia 14%, granulocytopenia 6%, and thrombocytopenia 6%. CONCLUSION: Palliation and survival compare favorably with other series, including many surgical series. The response findings encourage studies of both unresectable and (as neoadjuvant therapy) resectable tumors.

Adenocarcinoma↗

Pulmonary resection in the elderly.

PURPOSE OF REVIEW: With increasing longevity, altered demographics of the lung cancer population, and preoperative interventions to enhance the efficacy of surgical therapy, increasing numbers of elderly people will present for anesthesia and pulmonary resection. RECENT FINDINGS: The geriatric population often exhibits wide disparity between chronologic and physiologic senescence which is underscored by data indicating that outcome following lung resection for cancer is influenced more by tumor stage, preoperative functional status and comorbidities than age alone. Nonetheless, the normal process of cardiopulmonary aging can limit the physiological reserve necessary to compensate for perioperative stress even in otherwise healthy elderly patients. Data indicate a relatively favorable risk-benefit relationship for lung resection in the elderly given the poor prognosis for patients undergoing palliative care or chemotherapy or radiation alone. Emerging experience now suggests that minimally invasive surgical techniques for the treatment of lung cancer may parallel conventional thoracotomy in terms of oncologic efficacy while decreasing perioperative morbidity in the elderly. SUMMARY: The combination of an aging population, recent advances in neoadjuvant therapies, data supporting the oncologic efficacy of resection, and minimally invasive surgical techniques strongly suggests that more elderly patients will be candidates for surgical management of their lung cancer, thus presenting anesthesiologists with unique challenges.

Aged↗

Histopathologic analysis of angiogenic factors in localized renal cell carcinoma: the influence of neoadjuvant treatment.

BACKGROUND: This study was conducted in order to clarify whether histopathologic analysis of factor thymidine phosphorylase (TP) and Factor VIII could be a useful predictor of postoperative recurrence in localized renal cell carcinoma. Therefore, the relationship between tumor infiltrated lymphocytes (TIL) and both TP and Factor VIII was studied. METHOD: Of the 71 patients who underwent surgery, 54 patients had no neoadjuvant therapy (group 1), 10 patients were preoperatively administered IFN-gamma (group 2), and the remaining seven patients preoperatively received IFN-gamma and transarterial embolization (group 3). Both TP and Factor VIII immunostaining were performed on formalin-fixed, paraffin-embedded archival tissue from 71 renal cell carcinoma specimens, while TIL immunostaining was performed on frozen sections. Positive immunostaining was quantitatively scored by a computer-assisted digital image analysis. For TIL, positive results were semiquantitatively scored. RESULTS: A significant difference in the recurrence-free rate was recognized for Groups 1, 2 and 3 (P < 0.05). Therefore, the median TP-positive rate (PR), VIII-PR, number of microvessels and positive mean vascular area levels were investigated, between the recurrence cases (n = 6) and the recurrence-free cases (n = 11). Only the TP-PR levels showed a significant difference among them (P = 0.044). In regards to the neoadjuvant cases, a significant correlation was observed between both VIII-PR and CD4 (r = 0.815) as well as between VIII-PR and CD11b (r = 0.756). CONCLUSION: There was no clear evidence that the neoadjuvant treatment would increase the recurrence-free survival in patients with localized renal cell carcinoma. TP-PR might be a predictor of postoperative recurrence in patients with localized renal cell carcinoma.

Adult↗

Omission of bone scanning according to staging guidelines leads to futile therapy in non-small cell lung cancer.

The leading European and American professional societies recommend that bone scans (BS) should be performed in the staging of lung cancer only in those patients with bone pain. This prospective study investigated the sensitivity of conventional skeletal scintigraphy in detecting osseous metastases in patients with lung cancer and addressed the potential consequences of failure to use this method in the work-up of asymptomatic patients. Subsequent to initial diagnosis of non-small cell lung cancer, 100 patients were examined and questioned regarding skeletal complaints. Two specialists in internal medicine decided whether they would recommend a bone scan on the basis of the clinical evaluation. Skeletal scintigraphy was then performed blinded to the findings of history and physical examination. The combined results of magnetic resonance imaging (MRI) of the vertebral column, positron emission tomography (PET) of skeletal bone and the subsequent clinical course served as the gold standard for the identification of osseous metastases. Bone scintigraphy showed an 87% sensitivity in the detection of bone metastases. Failure to perform skeletal scintigraphy in asymptomatic patients reduced the sensitivity of the method, depending on the interpretation of the symptoms, to 19-39%. Without the findings of skeletal scintigraphy and the gold standard methods, 14-22% of patients would have undergone unnecessary surgery or neoadjuvant therapy. On this basis it is concluded that bone scans should not be omitted in asymptomatic patients.

Adult↗

Alternating hepatic arterial infusion and systemic chemotherapy for liver metastases from colorectal cancer: a phase II trial using intermittent percutaneous hepatic arterial access.

PURPOSE: To evaluate the objective response to a short course of hepatic arterial infusion (HAI) using temporary, percutaneously placed catheters alternating with systemic prolonged continuous infusion fluorouracil (ci 5-FU) and daily oral leucovorin (L). PATIENTS AND METHODS: Eligible patients were previously untreated (except for adjuvant therapy) adults with liver-predominant metastases, with Eastern Cooperative Oncology Group performance status of 0 to 2. Treatment regimen included HAI with fluorodeoxyuridine (FUDR) 60 mg/m2/d and L 15 mg/m2/d continuously infused daily for 4 days. After a 1-week rest, ci 5-FU was administered through a central venous access device using a dose of 180 mg/m2/d with a fixed dose of oral L at 5 mg/m2/d for 21 out of 28 days. Cycles were repeated every 6 weeks. After four cycles of therapy, patients were maintained on ci 5-FU and daily oral L until evidence of progression. RESULTS: Forty-three patients were enrolled onto this trial. One patient was ineligible. The objective response rate for all patients (17 partial, zero complete) was 41% (95% confidence interval [CI], 26% to 56%). Five patients were not able to receive at least one complete cycle of HAI. Among patients who received at least one complete cycle of HAI, the response rate was 46% (95% CI, 30% to 62%). Five patients underwent a liver resection after enrolling onto the protocol. At the time of analysis, estimated median time to progression was 6 months, and estimated median overall survival was 13 months. CONCLUSION: The objective response rate was comparable to that achieved with more prolonged and more frequent HAI using FUDR. This approach should be studied as an acceptable alternative to surgically placed hepatic arterial catheters/pumps and may have a role as neoadjuvant therapy for liver metastases that are unresectable, as well as an adjuvant role for patients with resected hepatic metastatic colorectal cancer.

Adult↗

PET scanning in lung cancer: current status and future directions.

Positron emission tomography (PET) represents a dramatic advance in the imaging of lung cancer. It is valuable for the diagnosis, staging, prognosis, and restaging of disease, and is most useful in patients considered for potentially curative therapy for non-small-cell lung cancer (NSCLC). In this work the current status and potential future applications of PET scanning in lung cancer are discussed. The relevant literature is also discussed, with an emphasis on studies with clinical applicability. Most of these studies involved the use of 18F-fluorodeoxyglucose (FDG). Numerous studies of the use of PET to assess undiagnosed pulmonary nodules have reported significant improvements in accurate diagnosis or exclusion of malignancy compared to conventional structural imaging alone. All of these studies, including metaanalysis, have shown that PET is more accurate than CT-based structural imaging in staging the mediastinum in surgical candidates. PET may have value in radiotherapy planning, and PET-based staging more accurately predicts survival in radiotherapy-treated patients than conventional staging. The rate of unsuspected distant metastasis detection in stage III disease exceeds 20%. PET also facilitates an accurate assessment of response in patients treated with radical chemoradiation or neoadjuvant therapy prior to surgery. PET has rapidly become an indispensable part of the evaluation of patients with potentially curable lung cancer; however, more work is required to define its role.

Combined Modality Therapy↗

Epithelial cells in bone marrow of oesophageal cancer patients: a significant prognostic factor in multivariate analysis.

The detection of epithelial cells in bone marrow, blood or lymph nodes indicates a disseminatory potential of solid tumours. 225 patients with squamous cell carcinoma of the oesophagus were prospectively studied. Prior to any therapy, cytokeratin-positive (CK) cells in bone marrow were immunocytochemically detected in 75 patients with the monoclonal anti-epithelial-cell antibody A45-B/B3 and correlated with established histopathologic and patient-specific prognosis factors. The prognosis factors were assessed by multivariate analysis. Twenty-nine of 75 (38.7%) patients with oesophageal cancer showed CK-positive cells in bone marrow. The analyses of the mean and median overall survival time showed a significant difference between patients with and without epithelial cells in bone marrow (P < 0.001). Multivariate analysis in the total patient population and in patients with curative resection of the primary tumour confirmed the curative resection rate and the bone marrow status as the strongest independent prognostic factors, besides the T-category. The detection of epithelial cells in bone marrow of oesophageal cancer patients is a substantial prognostic factor proved by multivariate analysis and is helpful for exact preoperative staging, as well as monitoring of neoadjuvant therapy.

Adult↗

Non-small-cell lung cancer (NSCLC): chemotherapy in advanced disease. Our experience in ten years.

This is a review of the therapeutic schedules used in our service during the past 10 years for the therapy of advanced non-small-cell lung cancer. During the first years, nonrandomized trials were conducted and several combinations were tested: MACC (methotrexate, doxorubicin, cyclophosphamide, and CCNU), cisplatin-etoposide, and cisplatin-vindesine. The results of these trials were invariably discouraging: objective responses hardly reached 30%, while the survival was around 15 months in the best case. On December 1985 a new randomized trial, based on the combination MIP (mytomicin, ifosfamide, cisplatin) was designed; 60.7% of objective responses were achieved, with 9 complete remissions (17.6%) and 22 partial remissions (43.1%). Median survival was 15 months. In order to reduce the toxicity of this combination, carboplatin was substituted for cisplatin. Unfortunately, results were very poor. No complete remission, and only 5 partial responses (20%) were achieved. At the present time, a new randomized trial is being conducted. In it, MIP combination is compared with VIP (vindesine, ifosfamide, cisplatin). Preliminary results have shown no differences between both arms in response, toxicity, or survival. New therapeutic approaches, as neoadjuvant therapy, are being explored.

Antineoplastic Combined Chemotherapy Protocols↗

[Clinical value of PET/CT for the diagnosis and management of lung nodules].

OBJECTIVE: To investigate the clinical value of 18F-fluorodeoxyglucose positron emission tomography (FDG PET)/CT for the diagnosis and management of lung nodules. METHODS: Twenty patients were evaluated: 15 with suspected cancer and 5 confirmed cancer. PET/CT scans were performed by discovery LS-PET/CT system. RESULTS: (1) The diagnostic accuracy of PET/CT was 100% in these 20 patients. Of 15 patients with suspected cancer, 7 were diagnosed as having benign disease and 8 malignant. All the 5 patients with confirmed cancer were all FDG positive. Of 11 single lesions on CT, 3 were positive by PET/CT images, 6 of 8 with positive CT images were diagnosed as having metastasis to the tissue outside the lung and the other 2 were metastatic. (2) After PET/CT scanning, the therapy scheme of 16 out of 20 patients were changed, and continual observation was practiced in 2, 3 were treated by anti-inflammation regimen, 2 by operation, 4 by local radiotherapy, 3 by chemotherapy only, 4 by radiotherapy plus chemotherapy or operation. (3) The radiotherapists made use of PET/CT fusion imaging for positioning in 8 patients who were indicated for radiotherapy. One of them who had received MM50 one course of intensity medulated conformal radiotherapy was re-examined by PET/CT after one and half months, the former parenchymal nodule disappeared and the glucose metabolism returned to normal. Two of them were finally operated after the surgeons have decided an operative approach on estimation of extent of lesion by the PET/CT fusion images. Pathological results showed no cancer cell involvement in the specimen margin or the local lymph nodes. CONCLUSION: (1) PET/CT is better in discriminating malignant from benign lung nodules than CT only. (2) PET/CT scanning facilitates an accurate assessment of response in clinical staging and neoadjuvant therapy scheme of lung cancer. (3) PET/CT fusion imaging provides an accurate biological target for radiotherapy and confirms the operation plan and extent of surgery.

Adult↗

Factor analysis as a means of determining response to chemotherapy in patients with osteogenic sarcoma.

The prognosis of localized osteogenic sarcoma (OS) has improved considerably since the introduction of neoadjuvant chemotherapy. However, there is a subset of patients who do not show full benefit from neoadjuvant chemotherapy because of chemoresistance. The early identification of poor responders to chemotherapy during neoadjuvant therapy remains difficult. In order to evaluate the role of bone scintigraphy we report our experience of dynamic technetium-99m hydroxymethylene diphosphonate bone scintigraphy in 19 cases of paediatric osteogenic sarcomas. Before the beginning of chemotherapy, a dynamic scan was recorded during 30 min followed by static images at 3 h. The procedure was repeated halfway through the course of chemotherapy (6th week). Histological grading of the response to chemotherapy was carried out in the 12th week, showing nine good responses and ten poor responses. Factor analysis of dynamic structures (FADS) applied to dynamic scans allowed us to identify three factors termed vascular, "soft tissue" and osseous factors. The effect of chemotherapy on each factor was evaluated. Using FADS we were able to detect all the poor histological responders with the combination of vascular and osseous factors. Six out of nine good histological responders were also classified as scintigraphic responders. FADS applied to dynamic bone scans allowed us to identify at an early stage all the poor histological responders to neoadjuvant chemotherapy. This method may have clinical relevance for the therapeutic strategy in patients with OS.

Adolescent↗

Adjuvant therapy in gastric and cardia cancer: should we irradiate?

PURPOSE OF REVIEW: The purpose of this review is to comment on the current status and the place of the (neo)adjuvant therapy of gastric cancer, and on the standardization of care in this setting. RECENT FINDINGS: The definition of optimal surgery remains controversial in gastric cancer. A recent review by the Dutch Gastric Cancer Group supports the so-called 'over-D1' extended lymphadenectomy, without pancreatectomy and splenectomy, as the optimal procedure, avoiding an increased postoperative mortality. The results from the phase III INT 116 trial should not definitively assign adjuvant chemoradiation as a robust standard of care, mainly due to the lack of optimal surgery in this trial. However, the concept of adjuvant chemoradiation will likely become more and more used, and will influence the design of future studies, reinforced by the incorporation of novel agents. If adjuvant chemotherapy failed to significantly increase survival, the use of perioperative chemotherapy (ECF regimen x 3 pre- and postoperative) was recently reported to improve survival, without affecting postoperative mortality and morbidity; mature results from this large phase III Medical Research Council Adjuvant Gastric Cancer Infusional Chemotherapy trial should be considered as an important step implementing neoadjuvant chemotherapy as a new standard of care. Neoadjuvant therapy of locally advanced tumors also offers an ideal setting to assess new combinations, including cytotoxics, biologics and conformational radiation, coupled with translational research. SUMMARY: Much remains to be done before anticipating an incontestable standard of care in gastric cancer, although the recent phase III trials indicate that multimodality therapy could impact on the prognosis of gastric cancer.

Chemotherapy, Adjuvant↗

Problems in pathologic staging of lung cancer.

CONTEXT: Tumor stage is the most important prognostic and predictive factor for patients with lung cancer, the most lethal neoplasm in the United States. It is used by thoracic surgeons, radiation therapists, and oncologists to determine whether patients with these neoplasms will be treated surgically with curative intent or with palliative radiation therapy and/or chemotherapy. OBJECTIVE: To review the variety of practical problems that can arise during the assessment of the pathologic stage and other prognostic/predictive factors included in the College of American Pathologist checklist for evaluation of resected lung neoplasms. DATA SOURCES: Potential practical difficulties that can arise during the pathologic staging of lung cancer patients include the distinction between pT1, pT2, and pT3 lesions based on their location and the presence of visceral pleura and/or parietal pleura invasion; the differential diagnosis between multiple synchronous or metachronous primary lung neoplasms (pT1m) and intrapulmonary metastasis of non-small cell carcinoma of the lung (pT4 or pM1 according to their location); and the role of the recent American Joint Committee on Cancer terminology for the classification of lymph nodes (isolated tumor cells, micrometastases, and metastases). CONCLUSIONS: The variety of practical problems that can arise during the assessment of important prognostic and predictive features such as resection margin status and evaluation of lymphovascular invasion are reviewed. A brief discussion of the assessment of the effects of neoadjuvant therapy on resected lung neoplasms is also included.

Humans↗

Prognostic factors predictive of survival for truncal and retroperitoneal soft-tissue sarcoma.

OBJECTIVE: The authors identified prognostic factors relevant to clinical outcomes (especially survival) in truncal and retroperitoneal soft-tissue sarcoma. SUMMARY BACKGROUND DATA: These results can be used to optimize surgical management and select patients most likely to benefit from novel therapeutic strategies in future trials. METHODS: A retrospective analysis was performed of a prospectively compiled database of 183 consecutive patients with truncal and retroperitoneal sarcomas seen at the Brigham and Women's Hospital and the Dana Farber Cancer Institute between 1970 to 1994. RESULTS: For truncal sarcoma, multivariate analysis showed that high-grade histology was associated with an eightfold increased risk of death compared with low-grade histology (p = 0.001). In addition to grade, gross positive margin of resection (p = 0.001), microscopic positive margin (p = 0.023), and tumors greater than 5 cm in size (p = 0.018) were important independent prognostic factors for survival. In this series, postoperative radiation therapy for truncal sarcoma was associated with a 2.4-fold decreased risk of death compared with truncal sarcoma patients receiving no adjuvant radiation therapy, having adjusted for the other prognostic factors (p = 0.030). In contrast, for retroperitoneal sarcoma, multivariate analysis showed that high-grade and intermediate-grade histology were associated with a five- to sixfold increased risk of death compared with low-grade histology (p = 0.009). In addition to grade, gross positive margin of resection (p = 0.001) and microscopic positive margin (p = 0.004) were important independent prognostic factors for survival in retroperitoneal sarcoma. Patients who received either preoperative or postoperative chemotherapy for retroperitoneal sarcoma had a 4.6-fold (p = 0.002) and 3-fold (p = 0.010) increased risk of death, respectively, compared with patients receiving no adjuvant chemotherapy, having adjusted for the other prognostic factors. CONCLUSIONS: The histologic grade and the margin of resection are prognostic for survival in both truncal and retroperitoneal soft-tissue sarcoma. Tumor size was an independent prognostic factor for truncal sarcoma, but not for retroperitoneal sarcoma. Postoperative adjuvant radiation was beneficial to overall survival for truncal sarcoma. In this series of patients receiving a heterogeneous mixture of chemotherapeutic regimens-either as preoperative "neoadjuvant" therapy or as postoperative "adjuvant" therapy, there were no beneficial effects on survival compared with nonrandomized patients not receiving chemotherapy.

Adult↗

Salvage radical prostatectomy: an alternative treatment for local recurrence of radioresistant cancer.

OBJECTIVES: The treatment of recurrent prostate cancer after radiotherapy or brachytherapy through radical prostatectomy has been little indicated due to the concern over the procedure's morbidity. We present the experience of our service with postradiotherapy radical prostatectomy. MATERIALS AND METHODS: Between 1996 and 2002, 9 patients submitted to radiotherapy due to prostate cancer were treated with salvage surgery for locally recurrent disease. All patients had a biopsy of the prostate confirming the tumor recurrence, increase in the PSA levels and staging without evidence of a systemic disease. We have assessed the morbidity and the recurrence-free survival rate after salvage radical prostatectomy. RESULTS: Preradiotherapy PSA varied from 6.2 to 50 ng/mL (mean 17.3) and clinical staging T1, T2 and T3 in 33.3%, 44.4% and 22.2% of the patients respectively. The interval for the biopsy after conforming external beam radiotherapy or brachytherapy varied from 8 to 108 months (median: 36). Four patients received antiandrogenic therapy neoadjuvant to the surgery with a mean of 7 months (1-48) after radiotherapy. From the six patients potent before the surgery, three have presented erectile dysfunction. Urinary incontinence as well as bladder neck sclerosis occurred in two patients (22.2%). Biochemical recurrence occurred in two individuals (22.2%) 12 months after the surgery. Biochemical recurrence-free survival rate was 77.8% with median follow-up time of 30 months (8-102). CONCLUSION: Salvage radical prostatectomy is a safe and effective alternative for the treatment of locally recurrent prostate cancer after radiotherapy and brachytherapy.

Aged↗