Day: 01/07/2012

Pulmonary metastasectomy in patients with renal cell carcinoma: a single-institution experience.

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Pulmonary metastasectomy in patients with renal cell carcinoma (RCC) remains controversial. The purpose of our analysis was to explore the outcome of patients with RCC who underwent pulmonary metastasectomy at our institution.

Methods

We reviewed data on 25 patients who underwent resection of lung metastasis from 1998 to 2008 at our institution.

Results

All patients were treated by radical nephrectomy for primary RCC. Progression-free survival (PFS) ranged from 0.3 to 198.8 months (median 7.4 months), and overall survival (OS) ranged from 2.4 to 198.8 months (median 33.9 months). The 5-year PFS rate was 24.9%, and the OS rate was 35.5%. Although differences in the resectability of the metastasectomy and OS were not significant in univariate or multivariate analyses, the relationship between PFS and the radicality of pulmonary metastasectomy was significant in both the univariate and multivariate analyses (P = 0.004, 0.012, respectively).

Conclusions

The results of pulmonary metastasectomy for patients with RCC at our institution indicate that pulmonary metastasectomy should be performed only when the pulmonary metastasis can be completely resected. Additional studies are therefore necessary to evaluate the prognostic factors and to determine the selection criteria for pulmonary metastasectomy in the new era of molecular-targeted agents.

Source: International Journal of Clinical Oncology

 

 

Anatomical study of the external carotid artery and its branches for administration of superselective intra-arterial chemotherapy via the superficial temporal artery

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.The branching patterns of the external carotid artery vary among individuals, and consideration of the proximity of nerves is important during catheter insertion in superselective intra-arterial infusion via the superficial temporal artery. We aimed to evaluate the anatomy of the external carotid artery and its surrounding nerves for safe and accurate administration of superselective intra-arterial chemotherapy via the superficial temporal artery.

Methods

We analyzed the external carotid artery and its branches morphometrically in 28 Japanese cadavers (56 sides).

Results

Vascular tortuosity in the preauricular region of the catheter insertion site was observed in 42.9% of the sides; the main trunk of the external carotid artery was excessively tortuous in 25.0% of the sides, primarily in the preparotid region. Faciolingual and superior thyrolingual trunks were observed in 28.6 and 1.8% of the sides, respectively. The superior thyroid, lingual, facial, occipital, and maxillary arteries branched from the external carotid artery above the carotid bifurcation in 41.1% of the sides. The mean distance between the insertion site and maxillary artery was 39.5 mm, indicating the extent of catheter insertion. The auriculotemporal nerve was observed near the superficial temporal artery in the preauricular region in 44.6% of the sides; however, the clearly identifiable nerves in the exposed area were difficult to avoid.

Conclusion

Because of the branching variations observed in individuals and sides, preoperative angiography is extremely important for avoiding complications.

Source: International Journal of Clinical Oncology

 

The prevalence of human papillomavirus in oral premalignant lesions and squamous cell carcinoma in comparison to cervical lesions used as a positive control .

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Previous reports concerning the prevalence of human papillomavirus (HPV) in oral squamous cell carcinoma (OSCC) have observed varied results. The aim of this study was to evaluate the prevalence of HPV in oral premalignant lesions (OPL) and OSCC. For accurate HPV detection in oral lesions, comparative analysis was performed on cervical lesions as positive controls.

Methods

Fifty-seven cases with OPL and 50 with OSCC were selected. Twenty-nine control cases were selected from cervical lesions. The HPV infection rate was analysed by consensus polymerase chain reaction (PCR) using the My09/My11 and Gp5+/Gp6+ primers, and genotyping detection was employed using a PCR-based micro-array. Immunohistochemical staining for p16INK4a was performed.

Results

Twenty-eight (96.6%) cases of cervical lesions were positive for HPV by consensus PCR and 24 cases (82.8%) were positive by genotyping. The total HPV-positive rate in cervical lesions was 96.6%. HPV-DNA was detected in nine cases (15.8%) of OPL and six cases (12.0%) of OSCC by consensus PCR. Six cases (10.5%) of OPL and three cases (6.0%) of OSCC were positive by genotyping. The total HPV-positive rate in oral lesions was 22.4% (26.3% of OPL and 18.0% of OSCC). In cervical lesions, immunohistochemistry of p16INK4a identified 27 cases (93.1%) as positive. Fifteen cases (26.3%) of OPL and eight cases (16.0%) of OSCC were positive for p16INK4a.

Conclusions

The HPV infection and p16INK4a-positive rates in oral lesions are lower than previously reported. This suggests that HPV may not play a major role in oral lesions although its involvement cannot completely be ruled out.

Source: International Journal of Clinical Oncology

 

A 4-week versus a 3-week schedule of gemcitabine monotherapy for advanced pancreatic cancer: a randomized phase II study to evaluate toxicity and dose intensity.

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This randomized phase II study compared the efficacy and toxicity between 4-week and 3-week schedules of gemcitabine monotherapy in advanced pancreatic cancer.

Methods

Patients with advanced pancreatic cancer were randomly assigned to either a 4-week schedule (gemcitabine at 1000 mg/m² as a 30-min infusion weekly for 3 consecutive weeks every 4 weeks) or a 3-week schedule (gemcitabine at 1000 mg/m² as a 30-min infusion weekly for 2 consecutive weeks every 3 weeks). The primary endpoint was the compliance rate during the first 8 weeks between the two groups.

Results

A total of 90 patients were enrolled. The compliance rate during the first 8 weeks was the same (53.3%). For the 4- and 3-week schedules, the tumor response rates were 14.2 and 17.1% (p = 0.92), median progression free survival was 112 and 114 days (p = 0.82), and median overall survival was 206 and 250 days (p = 0.84), respectively. Grade 3–4 neutropenia was the major adverse event in both schedules: 37.7 and 35.5% (p = 0.82). In contrast, thrombocytopenia (platelet count <70000/mm³) was significantly higher for the 4-week schedule: 26.6 and 4.4% (p = 0.008). The mean received dose intensity was equal: 588 and 550 mg/m²/week (p = 0.14).

Conclusions

The 3-week schedule of gemcitabine did not improve the compliance rate during 8 weeks compared with the 4-week schedule, but it attained a comparable efficacy with lower toxicity. Further investigation will be needed to introduce it into daily practice. Clinical trial registration number: UMIN ID 974.

Source: International Journal of Clinical Oncology

 

 

Surrogacy of tumor response and progression-free survival for overall survival in metastatic breast cancer resistant to both anthracyclines and taxanes.

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In breast cancer, the validity of surrogate endpoints for overall survival (OS) is a matter of controversy.

Methods

In order to generate a hypothesis, we evaluated whether tumor response or progression-free survival (PFS) could be valid surrogates for OS in patients with metastatic breast cancer. Data from 30 patients were available from a phase II study of trastuzumab and capecitabine in human epidermal growth factor receptor 2-overexpressing metastatic breast cancer resistant to both anthracyclines and taxanes. The proportional hazards (PH) model was applied to evaluate the relationship between OS and tumor response or PFS. In addition, to explore prognostic factors influencing OS or post-progression survival, the PH model with a stepwise regression procedure was applied.

Results

The relationship between tumor response and PFS was highly significant (P = 0.0036); however, there was no significant relationship between tumor response and OS or between PFS and OS. In the multivariate analysis, the sum of the longest diameter of target lesions (P = 0.0011), neutrophil count (P = 0.0033), and creatinine (P = 0.0085) were statistically significantly associated with OS.

Conclusion

We generated a hypothesis that neither PFS nor tumor response were valid as surrogate endpoints for OS, at least in the phase II trial for metastatic breast cancer resistant to both anthracyclines and taxanes. We also found that the sum of the longest diameter of target lesions, neutrophil count, and creatinine were prognostic factors for OS.

Source: International Journal of Clinical Oncology

 

 

Targeted Therapies for Adrenocortical Carcinoma: IGF and Beyond.

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Standard chemotherapy for adrenocortical cancer currently is under evaluation in the context of the recently completed FIRM-ACT evaluating the combination of mitotane with either streptozocin or etoposide, cisplatin, and doxorubicin. New agents are eagerly sought by the ACC community that hopes to make progress against this deadly disease. Investigators have begun to dissect the molecular and genomic context of ACC with a goal of identifying potential novel therapeutic agents. One gene consistently overexpressed in ACC is insulin growth factor type 2. Targeting its receptor IGF1R has shown encouraging results in ACC cell lines and against murine xenografts. As a result, clinical trials to evaluate agents targeting the IGF1R have been done including mitotane and IMC-A12 (a monoclonal antibody) and the GALACCTIC trial that has just completed accrual to evaluate OSI-906, a small molecule IGF1R antagonist. On the horizon are other agents targeting other tyrosine kinases, including EGF and FGF, and novel strategies such as individualized tumor analysis to select treatment.

 

Source: Hormones and Cancer

 

Metronomic Therapy Concepts in the Management of Adrenocortical Carcinoma.

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Metronomic chemotherapy is the administration of cytotoxic drugs at low doses, on a frequent or continuous schedule, with no extended interruption. This treatment approach can target tumor cells indirectly since it can affect the endothelium of the growing tumor vasculature and stimulates the anticancer immune response. Both the antiangiogenetic and the immunomodulatory roles of metronomic chemotherapy favor a tumor dormancy, a condition that may improve the patient outcome. Prospective clinical trials conducted in several malignancies have shown that metronomic chemotherapy can obtain disease stabilization or responses in tumors that had been made resistant in vivo to conventional chemotherapeutic regimens. Three prospective phase II trials have been conducted in patients with adrenocortical carcinoma (ACC). In all of them, patients heavily pretreated with conventional chemotherapy and mitotane have been enrolled. One trial tested the activity of the association of gemcitabine and fluoropyrimidines administered on a metronomic schedule. In this trial, 40% of patients attained a disease stabilization or disease response that was long lasting in some of them. In the remaining two trials, metronomic chemotherapy was administered in association with antiangiogenetic drugs, and the results were disappointing since no response or stable disease was obtained. In conclusion, metronomic chemotherapy can delay tumor progression in advanced ACC and deserves to be further tested. The concomitant administration of antiangiogenetic drugs may be detrimental. Several important questions remain to be addressed such as the optimal dose and most effective dosing interval, when to use the metronomic approach in the natural history of the disease, the choice of cytotoxic drugs, and the most efficacious way to integrate metronomic chemotherapy with standard therapy protocols.

 

Source: Hormones and Cancer

 

 

 

A debate on laparoscopic versus open adrenalectomy for adrenocortical carcinoma.

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Adrenocortical cancer (ACC) is a rare disease that is difficult to treat. Surgery remains the primary treatment modality and the only chance for cure in these patients. Since the early 1990s, laparoscopic adrenalectomy (LA) has replaced open adrenalectomy (OA) as the gold standard for addressing adrenal disorders of benign origin; however, the oncologic effectiveness of laparoscopic adrenalectomy for resection of primary adrenocortical malignancies remains unclear. Since the initial consensus statement from the International Adrenal Cancer Symposium held in Ann Arbor, MI in 2003, a number of studies have investigated the question of equivalence of LA compared to OA for ACC. Several controversial topics were debated during the 3rd International Adrenal Cancer Symposium held in Wurzburg, Germany in 2011. This debate sought to review the advantages and disadvantages of OA versus LA and review findings of recent studies related to the topic. As all studies involving this topic have methodological flaws, some more than others, the results of each study must be interpreted with caution. In conclusion, this debate will undoubtedly continue well into the future; however, it is clear that an oncologically appropriate surgical resection is of the utmost importance for the treatment of ACC and there is only one chance to achieve this. Poor outcomes will result from inadequate surgery, whether performed by an open or laparoscopic approach. Therefore, there is no doubt that surgery for suspected ACC should only be performed in specialized centers.

 

Source: Hormones and Cancer

 

 

FDG PET in the Management of Patients with Adrenal Masses and Adrenocortical Carcinoma

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Adrenocortical carcinoma (ACC) is a rare tumor with aggressive behavior, high recurrence rate, and rapid evolution. Surgery is the only curative modality, while systemic treatments such as mitotane and chemotherapy associated to locoregional therapeutic tools remain as palliative options. Imaging has an important role in the management of patients with ACC both at diagnosis and during follow-up. First, it is necessary to characterize undetermined adrenal masses, selecting patients for surgery. Then, in case of malignancy, it is mandatory to assess disease extension, to detect early relapse during follow-up, and to evaluate treatment response. Computed tomography scan and magnetic resonance imaging are actually the most used techniques for these intents as they are widely available in clinical practice. 18F-fluorodeoxyglucose positron emission tomography (FDG PET) is routinely used for other malignancies and, on the basis of published data, is also becoming a promising tool in the management of ACC. Not only is it a diagnostic tool complementary to morphological imaging in the characterization of adrenal masses and in tumoral lesions detection, but it can be also useful to evaluate tumor response to treatment. New tracers and indications for the clinical US.

Source: Hormones and Cancer

 

Hypertonic saline for treating raised intracranial pressure: literature review with meta-analysis A review.

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Currently, mannitol is the recommended first choice for a hyperosmolar agent for use in patients with elevated intracranial pressure (ICP). Some authors have argued that hypertonic saline (HTS) might be a more effective agent; however, there is no consensus as to appropriate indications for use, the best concentration, and the best method of delivery. To answer these questions better, the authors performed a review of the literature regarding the use of HTS for ICP reduction.

Methods

A PubMed search was performed to locate all papers pertaining to HTS use. This search was then narrowed to locate only those clinical studies relating to the use of HTS for ICP reduction.

Results

A total of 36 articles were selected for review. Ten were prospective randomized controlled trials (RCTs), 1 was prospective and nonrandomized, 15 were prospective observational trials, and 10 were retrospective trials. The authors did not distinguish between retrospective observational studies and retrospective comparison trials. Prospective studies were considered observational if the effects of a treatment were evaluated over time but not compared with another treatment.

Conclusions

The available data are limited by low patient numbers, limited RCTs, and inconsistent methods between studies. However, a greater part of the data suggest that HTS given as either a bolus or continuous infusion can be more effective than mannitol in reducing episodes of elevated ICP. A meta-analysis of 8 prospective RCTs showed a higher rate of treatment failure or insufficiency with mannitol or normal saline versus HTS.

Source: Journal of Neurosurgery