Aruna Turaka

Hypoxic prostate/muscle PO2 ratio predicts for outcome in patients with localized prostate cancer: long-term results.

PURPOSE To correlate tumor oxygenation status with long-term biochemical outcome after prostate brachytherapy. METHODS AND MATERIALS Custom-made Eppendorf PO(2) microelectrodes were used to obtain PO(2) measurements from the prostate (P), focused on positive biopsy locations, and normal muscle tissue (M), as a control. A total of 11,516 measurements were obtained in 57 men with localized prostate cancer immediately before prostate brachytherapy was given. The Eppendorf histograms provided the median PO(2), mean PO(2), and % <5 mm Hg or <10 mm Hg. Biochemical failure (BF) was defined using both the former American Society of Therapeutic Radiation Oncology (ASTRO) (three consecutive raises) and the current Phoenix (prostate-specific antigen nadir + 2 ng/mL) definitions. A Cox proportional hazards regression model evaluated the influence of hypoxia using the P/M mean PO(2) ratio on BF. RESULTS With a median follow-up time of 8 years, 12 men had ASTRO BF and 8 had Phoenix BF. On multivariate analysis, P/M PO(2) ratio <0.10 emerged as the only significant predictor of ASTRO BF (p = 0.043). Hormonal therapy (p = 0.015) and P/M PO(2) ratio <0.10 (p = 0.046) emerged as the only independent predictors of the Phoenix BF. Kaplan-Meier freedom from BF for P/M ratio <0.10 vs. ≥0.10 at 8 years for ASTRO BF was 46% vs. 78% (p = 0.03) and for the Phoenix BF was 66% vs. 83% (p = 0.02). CONCLUSIONS Hypoxia in prostate cancer (low mean P/M PO(2) ratio) significantly predicts for poor long-term biochemical outcome, suggesting that novel hypoxic strategies should be investigated.

A better prognosis for Merkel cell carcinoma of unknown primary origin

BACKGROUND There is limited evidence that Merkel cell carcinoma (MCC) arising from a nodal basin without evidence of a primary cutaneous (PC) site has better prognosis. We present our experience at 2 tertiary care referral centers with stage III MCC with and without a PC site. METHODS Fifty stage III MCC patients were identified between 1996 and 2011. Clinical data were analyzed, with primary endpoints being disease-free survival and overall survival. RESULTS Of stage III patients, 34 patients presented with a PC site and 16 patients with an unknown primary (UP) site. Treatment strategies varied; of patients with UP vs. PC sites, 25% vs. 44% underwent combined regional lymphadenectomy and radiation, with an additional 25% vs. 15% receiving chemotherapy. The median disease-free survival for a UP site was not reached vs. 15 months for a PC site (hazards ratio = .48, P = .18). The median overall survival for a UP site was not reached vs 21 months for a PC site (hazards ratio = .34, P = .03). Multivariate analysis showed that UP status was a significant factor in overall survival (P = .002). CONCLUSIONS Stage III MCC with a UP site portends a better prognosis than MCC with a PC site.

Young age is not associated with increased local recurrence for DCIS treated by breast-conserving surgery and radiation†

We report local recurrence (LR) after breast‐conserving surgery and radiation (BCS + RT) for ductal carcinoma in situ (DCIS) to determine outcomes for patients aged ≤40 years compared with older women.

Increased recurrences using intensity-modulated radiation therapy in the postoperative setting

Purpose:To determine the pattern of failures following intensity modulated radiation therapy for head and neck cancer. Material and Methods:A retrospective single institution study. Between May 2001 and June 2008, 176 patients with head and neck cancer were treated with intensity modulated radiation therapy at Fox Chase Cancer Center. Ninety-five (54%) were squamous cell carcinoma treated with curative intent. Tumor and nodal stage, tobacco history, definitive versus postoperative therapy (PORT), addition of chemotherapy and RT duration were analyzed for association with patterns of failure. In patients treated with definitive radiation, high-risk PTV (PTV1) was prescribed to 70 Gy and low-risk PTV (PTV2) to 56 Gy. In the PORT setting, PTV1 was prescribed to 60 to 66 Gy and PTV2 to 54 Gy. Patterns of failure were assessed. Local failure (LF) was defined as the persistence of disease or recurrence within PTV1, marginal failure as recurrence at the region of high-dose falloff, and regional failure as nodal recurrence within PTV2. Results:Median follow-up was 20 months (range: 1–117). Median age was 60 years (range: 28–88), with 80% smokers and 81% stage III or IV. PORT was given to 29% and 71% were treated definitively, with concurrent Cisplatin used in the majority. Three-year local and locoregional (LR) failure rates were 9% and 16%, respectively. Failures occurred in 14 patients: 8 local, 3 regional, 1 LR, and 2 distant. Five of the 8 LF and all 3 marginal failures were observed in PORT cohort. On univariate analysis, the only predictor of LF was the use of PORT (P = 0.06). LR control was 66% for PORT versus 87%, 97% for definitive RT and chemoRT. Conclusions:Local, regional failures were more common following PORT related to an increased risk of marginal failures.

Absolute lymphocyte count: A potential prognostic factor for Merkel cell carcinoma

BACKGROUND Absolute lymphocyte count (ALC) is a laboratory value commonly obtained during workup of patients with Merkel cell carcinoma (MCC). OBJECTIVE We report the prognostic impact of ALC as a surrogate of immune status in MCC. METHODS A complete blood cell count was available for 64 patients with MCC in the month before definitive surgery, chemotherapy, or radiation. Statistical analysis was performed with classification and regression tree analysis, log rank test, and Cox model. RESULTS Median overall survival (OS) for the cohort was 97 months. Median OS for patients with an ALC less than 1.1 k/mm(3) was 18.8 versus 110.1 months for those with ALC greater than or equal to 1.1 k/mm(3) (P = .002, hazard ratio 0.29). Multivariate analysis of OS controlling for ALC, sex, stage, adjuvant chemotherapy, hematologic malignancy, and immunosuppression demonstrated ALC as a prognostic factor (P = .03). Disease-free survival at 36 months for ALC less than 1.1 k/mm(3) was 26.9% versus 64.4% for those with ALC greater than or equal to 1.1 k/mm(3) (P = .01). ALC was not a significant predictor for disease-free survival on multivariate analysis (P = .12). LIMITATIONS This is a single-institution retrospective data set. CONCLUSION ALC is associated with OS but not disease-free survival in MCC using a threshold of less than 1.1 k/mm(3). This test may provide additional prognostic information for patients with MCC.

Surgery in the Multimodality Treatment of Sinonasal Malignancies

M alignancies of the paranasal sinuses represent a rare and biologically heterogeneous group of cancers. Understanding of tumor biology continues to evolve and will likely facilitate the development of improved treatment strategies. For example, some sinonasal tumors may benefit from treatment through primarily nonsurgical approaches, whereas others are best addressed through resection. The results of clinical trials in head and neck cancer may not be generalizable to this heterogeneous group of lesions, which is defined anatomically rather than through histogenesis. Increasingly sophisticated pathologic assessments and the elucidation of molecular markers, such as the human papilloma virus (HPV), in sinonasal cancers have the potential to transform the clinical management of these malignant neoplasms. Published reports often suggest that treatment approaches that include surgery result in better local control and survival. However, many studies are marked by selection bias. The availability of effective reconstruction makes increasingly complex procedures possible, with improved functional outcomes. With advances in surgery and radiation, the multimodal treatment of paranasal sinus cancers is becoming safer. The use of chemotherapy remains a subject of active investigation.

Predictors and management of chest wall toxicity after lung stereotactic body radiotherapy.

Stereotactic body radiotherapy is the preferred treatment modality for patients with inoperable early stage lung cancer. Chest wall toxicity is a potentially dose limiting side effect and may include fractures or pain secondary to treatment. The pathophysiology of these symptoms is unclear although it is presumed that radiation may alter the bones normal tissue environment, affecting maintenance and remodeling. Chest wall pain is likely neuropathic secondary to injury to the intercostal nerves. Identifying patients with chest wall toxicity can be difficult due to the varying definitions of toxicity as well as heterogeneous contouring guidelines. Multiple studies have demonstrated a correlation between treatment factors and the incidence of chest wall toxicity. An increase in dose and treatment volume appear to be the most consistent radiation factors associated with toxicity. Patient factors such as body mass index, female gender, tumor location, and age have also been correlated with an increased likelihood of developing side effects. Management of chest wall toxicity is typically conservative using analgesic medications although surgical intervention may be required for displaced fractures. In this review, we examine the treatment, patient, and tumor factors predictive for chest wall toxicity and the implications for the treating physician.

Multidisciplinary therapy of stage IIIA non-small-cell lung cancer: Long-term outcome of chemoradiation with or without surgery

BACKGROUND Stage IIIA non-small-cell lung cancer (NSCLC) is highly heterogeneous due to differences in the size of the primary tumor and the extent and location of nodal disease. Although the addition of surgery to chemoradiation did not improve overall survival (OS) for stage IIIA patients in a randomized intergroup trial (INT 0139), subset analyses of the trial suggest that a trimodality approach incorporating lobectomy may be superior to bimodality therapy with chemoradiation alone. METHODS We analyzed the outcomes of patients with stage IIIA NSCLC (T3N1, T1-3N2) treated at our center between January 2000 and December 2008. We compared OS for those undergoing definitive chemoradiation to those undergoing chemoradiation followed by either lobectomy or pneumonectomy. Demographic variables were balanced by propensity score analysis method. RESULTS In our analysis of 249 patients, the median age was 65 years, 43% were men, and 96.5% had N2 disease. Chemoradiation followed by lobectomy yielded superior OS compared with chemoradiation (median OS 39 months vs 22 months, P = .038 after propensity score adjustment). There was no significant survival benefit for pneumonectomy over chemoradiation (median survival 28 months vs 22 months, P = .534). CONCLUSIONS Our data corroborate the findings of the INT 0139 trial. We propose that a formal randomized trial be performed comparing chemoradiation followed by lobectomy vs definitive chemoradiation in patients with stage IIIA disease whose tumors are resectable by lobectomy. Our data do not support the incorporation of pneumonectomy in the management of stage IIIA patients with N2 disease.

Radiation therapy for pituitary metastasis: report of four cases.

AIMS AND BACKGROUND To report the clinical outcomes of four patients with pituitary metastases treated with radiotherapy. METHODS Retrospective chart review of four cases. RESULTS The mean age of the patients was 66 years; two were women and two were men. The mean duration of symptoms at initial presentation of the primary tumor was 2.25 months. The location of the primary tumor was the breast in one case and the lung in three. Magnetic resonance imaging of the brain revealed sellar masses in all cases. The mean interval between the primary tumor diagnosis and the development of pituitary metastases was 22.5 months. The metastases were treated with radiation therapy (palliative/stereotactic/intensity modulated) at a mean dose of 3219 cGy. At the last follow-up, three patients were dead and one was alive. CONCLUSIONS Treatment with three-dimensional conformal radiotherapy or stereotactic radiotherapy is a suitable non-surgical option for patients with pituitary metastases.

Metastatic small-cell lung carcinoma to the thyroid gland: a case report

Object: Metastasis to the thyroid gland is a rare event. Methods: We describe an unusual case of a 38-year-old woman with a history of small-cell lung cancer (SCLC), presenting with a new nodule in the thyroid gland, found to be metastatic SCLC, without evidence of widespread dissemination. Conclusions: A new thyroid nodule should be carefully evaluated for metastasis in a patient with a history of prior malignancy.