The effect of dose escalation for large squamous cell carcinomas of the anal canal

Purpose: Chemoradiation allows for organ preservation in patients with anal cancer, but patients with large tumors (> 5 cm) have elevated rates of locoregional recurrence. With conformal radiation techniques, there is interest in dose escalation to decrease local recurrence in patients with large tumor size. Methods/patients: The National Cancer Database (NCDB) was used to identify patients with anal cancer from 2004 to 2013 with tumors > 5 cm. Adult patients who received definitive chemoradiation were included. Patients with prior resection were excluded. High dose was defined as greater than or equal to 5940 cGy. Statistical analyses were performed using logistic regression, Kaplan-Meier, and Cox proportional hazards for overall survival (OS). Results: In total, 1349 patients were analyzed with 412 (30.5%) receiving high-dose radiation therapy (RT). 5-year OS was 58 and 60% for high and standard dose RT, respectively (p = 0.9887). On univariate analysis, high-dose RT was not associated with improved OS (HR = 0.998, CI 0.805-1.239, p = 0.9887). On multivariate analysis, high-dose RT (HR = 0.948, CI 0.757-1.187, p = 0.6420) was not associated with improved OS but older age (HR = 1.535, CI 1.233-1.911, p = 0.0001), male sex (HR = 1.695, CI 1.382-2.080, p < 0.0001), comorbidities (HR = 1.389, CI 1.097-1.759, p = 0.0064), and long RT (HR = 1.299, CI 1.047-1.611, p = 0.0173) were significantly associated with decreased OS. Conclusions: There was no observed difference in OS for dose escalation of anal cancers > 5 cm in this population-based analysis. Differences in local control and salvage therapy cannot be assessed through the NCDB. Whether dose escalation of large tumors may improve local control and colostomy-free survival remains an important question and is the subject of ongoing trials

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The absolute volume of PET-defined, active bone marrow spared predicts for high grade hematologic toxicity in cervical cancer patients undergoing chemoradiation

Introduction: Hematologic toxicity (HT) in cervical cancer patients can cause treatment delays and reduction in chemotherapy, especially in high risk patients. Dose to PET-defined regions of active bone marrow (ABM) has been shown to correlate with cytopenias. An absolute volume of ABM spared may accurately represent hematopoietic reserve and risk of HT. This analysis evaluates whether the volume of ABM spared can more accurately predict HT compared to conventional dosimetric parameters. Methods: Thirty-one patients treated for cervical cancer with chemoradiation from 9/2011 to 8/2016 were retrospectively reviewed. Receiver operating characteristic (ROC) curve were used to assess optimal cutpoint criterions for grade 3+ HT based on the CTCAEv4. Conventional dosimetric parameters to PBM and ABM (mean dose, V10, V20, V40) were assessed as well as the absolute volume (cc) of PBM and ABM spared 10, 20, and 40 Gy. Results: The absolute volume of PBM spared 10 Gy (< 230 cc; AUC 0.732, p = 0.03) as well as volume of ABM spared 10 Gy (< 179 cc; AUC 0.815, p = 0.0002), spared 20 Gy (< 186 cc; AUC 0.774, p = 0.0015), and spared 40 Gy (< 738 cc; AUC 0.887, p < 0.0001) all predicted grade 3+ HT. In patients with < 738 cc of ABM spared 40 Gy, 18/18 (100%) had grade 3+ toxicity compared to 6/13 (46%) of patients with > 738 cc of ABM spared 40 Gy (p < 0.0001). Conclusion: The baseline volume of ABM and the fraction of ABM present in patients vary significantly. The ongoing NRG-GY006 trial and other efforts at bone marrow sparing use V10, V20, and mean dose to the ABM during planning optimization. This analysis suggests that the volume of ABM spared 40 Gy (> 738 cc) may be a stronger predictor of HT than conventional dosimetric parameters. This should be further evaluated for clinical use

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The effect of dose escalation for large squamous cell carcinomas of the anal canal.

PURPOSE: Chemoradiation allows for organ preservation in patients with anal cancer, but patients with large tumors (> 5 cm) have elevated rates of locoregional recurrence. With conformal radiation techniques, there is interest in dose escalation to decrease local recurrence in patients with large tumor size. METHODS/PATIENTS: The National Cancer Database (NCDB) was used to identify patients with anal cancer from 2004 to 2013 with tumors > 5 cm. Adult patients who received definitive chemoradiation were included. Patients with prior resection were excluded. High dose was defined as greater than or equal to 5940 cGy. Statistical analyses were performed using logistic regression, Kaplan-Meier, and Cox proportional hazards for overall survival (OS). RESULTS: In total, 1349 patients were analyzed with 412 (30.5%) receiving high-dose radiation therapy (RT). 5-year OS was 58 and 60% for high and standard dose RT, respectively (p = 0.9887). On univariate analysis, high-dose RT was not associated with improved OS (HR = 0.998, CI 0.805-1.239, p = 0.9887). On multivariate analysis, high-dose RT (HR = 0.948, CI 0.757-1.187, p = 0.6420) was not associated with improved OS but older age (HR = 1.535, CI 1.233-1.911, p = 0.0001), male sex (HR = 1.695, CI 1.382-2.080, p < 0.0001), comorbidities (HR = 1.389, CI 1.097-1.759, p = 0.0064), and long RT (HR = 1.299, CI 1.047-1.611, p = 0.0173) were significantly associated with decreased OS. CONCLUSIONS: There was no observed difference in OS for dose escalation of anal cancers > 5 cm in this population-based analysis. Differences in local control and salvage therapy cannot be assessed through the NCDB. Whether dose escalation of large tumors may improve local control and colostomy-free survival remains an important question and is the subject of ongoing trials.

The absolute volume of PET-defined, active bone marrow spared predicts for high grade hematologic toxicity in cervical cancer patients undergoing chemoradiation.

INTRODUCTION: Hematologic toxicity (HT) in cervical cancer patients can cause treatment delays and reduction in chemotherapy, especially in high risk patients. Dose to PET-defined regions of active bone marrow (ABM) has been shown to correlate with cytopenias. An absolute volume of ABM spared may accurately represent hematopoietic reserve and risk of HT. This analysis evaluates whether the volume of ABM spared can more accurately predict HT compared to conventional dosimetric parameters. METHODS: Thirty-one patients treated for cervical cancer with chemoradiation from 9/2011 to 8/2016 were retrospectively reviewed. Receiver operating characteristic (ROC) curve were used to assess optimal cutpoint criterions for grade 3+ HT based on the CTCAEv4. Conventional dosimetric parameters to PBM and ABM (mean dose, V10, V20, V40) were assessed as well as the absolute volume (cc) of PBM and ABM spared 10, 20, and 40 Gy. RESULTS: The absolute volume of PBM spared 10 Gy (< 230 cc; AUC 0.732, p = 0.03) as well as volume of ABM spared 10 Gy (< 179 cc; AUC 0.815, p = 0.0002), spared 20 Gy (< 186 cc; AUC 0.774, p = 0.0015), and spared 40 Gy (< 738 cc; AUC 0.887, p < 0.0001) all predicted grade 3+ HT. In patients with < 738 cc of ABM spared 40 Gy, 18/18 (100%) had grade 3+ toxicity compared to 6/13 (46%) of patients with > 738 cc of ABM spared 40 Gy (p < 0.0001). CONCLUSION: The baseline volume of ABM and the fraction of ABM present in patients vary significantly. The ongoing NRG-GY006 trial and other efforts at bone marrow sparing use V10, V20, and mean dose to the ABM during planning optimization. This analysis suggests that the volume of ABM spared 40 Gy (> 738 cc) may be a stronger predictor of HT than conventional dosimetric parameters. This should be further evaluated for clinical use.