Does kV Image Guidance for Bone Metastases Improve Pain Control?

PURPOSE/OBJECTIVES: Despite its widespread availability, the use of kilovoltage (kV) image guidance is often related to factors such as perceived adequacy of clinical patient setup and individual practice patterns. We sought to determine whether kV image guidance in the treatment of painful bone metastases would improve therapeutic efficacy. MATERIALS/METHODS: Under an Institutional Review Board approved protocol, hospital records of 164 patients having received radiation therapy to 257 individual painful osseous metastases were retrospectively reviewed. Marginal logistic regression analyses using the generalized estimating equation (GEE) approach were used to investigate potential associations between pain reduction and several patient, disease, and treatment related variables. Correlation of kV image guidance with pain reduction was analyzed by univariate and multivariate GEE logistic regression analysis. RESULTS: Median time to pain reduction was 3 days (range 0~109 days) from the start of radiation therapy. Pain reduction ≥ 50% was noted in 196 (77%) metastatic lesions with 136 (53%) demonstrating complete pain relief. Patients with metastatic lesions from non-small cell lung cancer experienced less pain relief (p = 0.007). Disease extension outside of bone was a negative predictor for pain reduction (p = 0.02). On univariate and multivariate logistic regression, kV image guidance demonstrated a statistically significant correlation with improved pain control in cases involving treatment of the lower extremities (p = 0.03) and those with fewer treatment fractions (p = 0.01), particularly in the setting of extra-osseous disease extension (p = 0.003). CONCLUSIONS: Kilovoltage image guidance in the treatment of painful bone metastases may offer greater pain control through improved patient setup, particularly for patients with tumors of the lower extremities, extraosseous disease extension, and fewer treatment fractions.

Overall survival advantage of chemotherapy and radiotherapy in the perioperative management of large extremity and trunk soft tissue sarcoma; a large database analysis.

PURPOSE: Intergroup 9514 reported promising outcomes with neoadjuvant chemoradiotherapy for large extremity/trunk soft tissue sarcoma (ESTS). One decade later, optimum integration of chemotherapy and radiotherapy into the perioperative management of ESTS remains to be defined. METHODS: The National Cancer Data Base was used to identify 3422 patients who underwent resection for large (>8cm) high-grade STS between 2004 and 2013. Chi-square analysis was used to evaluate distribution of patient and tumor related factors within treatment groups while multivariate analyses were used to determine the impact of these factors on patient outcome. The Kaplan Meier method and Cox proportional hazards model were utilized to evaluate overall survival according to treatment regimen, with a secondary analysis based on propensity score matching to control for prescription bias and potential confounders imbalance. RESULTS: Hazard ratio for death was reduced by 35% with radiotherapy and 24% with chemotherapy, compared to surgery alone. Combination therapy incorporating both modalities improved 5-yr survival (62.1%) compared to either treatment alone (51.4%). The sequencing of chemotherapy and radiotherapy or whether they were delivered as adjuvant vs. as neoadjuvant therapy did not affect their efficacy. Age>50years, tumor size>11cm, and tumor location on the trunk/pelvis were poor prognostic factors. CONCLUSION: Our analysis suggests that adjunctive modalities are both critical in the treatment of large high-grade ESTS, improving survival when used individually and demonstrating synergy in combination, regardless of sequencing relative to each other or relative to surgery; thus providing a framework for future randomized trials.

Dose-painted intensity modulated radiation therapy improves local control for locally advanced pancreas cancer.

Background. To evaluate the outcomes, adverse events, and therapeutic role of Dose-Painted Intensity-Modulated Radiation Therapy (DP-IMRT) for locally advanced pancreas cancer (LAPC). Methods. Patients with LAPC were treated with induction chemotherapy (n = 25) and those without metastasis (n = 20) received DP-IMRT consisting of 45 Gy to Planning Treatment Volume 1 (PTV1) including regional lymph nodes with a concomitant boost to the PTV2 (gross tumor volume + 0.5 cm) to either 50.4 Gy (n = 9) or 54 Gy (n = 11) in 25 fractions. DP-IMRT cases were compared to three-dimensional conformal radiation therapy (3D-CRT) plans to assess the potential relationship of radiation dose to adverse events. Kaplan-Meier and Cox regression analyses were used to calculate survival probabilities. The Fisher exact test and t-test were utilized to investigate potential prognostic factors of toxicity and survival. Results. Median overall and progression-free survivals were 11.6 and 5.9 months, respectively. Local control was 90%. Post-RT CA-19-9 levels following RT were predictive of survival (P = 0.02). Grade 2 and ≥grade 3 GI toxicity were 60% and 20%, respectively. In comparison to 3D-CRT, DP-IMRT plans demonstrated significantly lower V45 values of small bowel (P = 0.0002), stomach (P = 0.007), and mean liver doses (P = 0.001). Conclusions. Dose-escalated DP-IMRT offers improved local control in patients treated with induction chemotherapy for LAPC. Radiation-related morbidity appears reduced with DP-IMRT compared to 3D-CRT techniques, likely due to reduction in RT doses to organs at risk.

Intensity-modulated radiation therapy for rectal carcinoma can reduce treatment breaks and emergency department visits.

Purpose. To compare the acute toxicities of IMRT to 3D-conformal radiation therapy (3DCRT) in the treatment of rectal cancer. Methods and Materials. Eighty-six patients with rectal cancer preoperatively treated with IMRT (n = 30) and 3DCRT (n = 56) were retrospectively reviewed. Rates of acute toxicity between IMRT and 3DCRT were compared for anorexia, dehydration, diarrhea, nausea, vomiting, weight loss, radiation dermatitis, fatigue, pain, urinary frequency, and blood counts. Fisher's exact test and chi-square analysis were applied to detect statistical differences in incidences of toxicity between these two groups of patients. Results. There were fewer hospitalizations and emergency department visits in the group treated with IMRT compared with 3DCRT (P = 0.005) and no treatment breaks with IMRT compared to 20% with 3DCRT (P = 0.0002). Patients treated with IMRT had a significant reduction in grade ≥3 toxicities versus grade ≤2 toxicities (P = 0.016) when compared to 3DCRT. The incidence of grade ≥3 diarrhea was 9% among 3DCRT patients compared to 3% among IMRT patients (P = 0.31). Conclusions. IMRT for rectal cancer can reduce treatment breaks, emergency department visits, hospitalizations, and all grade ≥3 toxicities compared to 3DCRT. Further evaluation and followup is warranted to determine late toxicities and long-term results of IMRT.

Real-time fluorescent resonance energy transfer analysis to monitor drug resistance in chronic myelogenous leukemia.

Despite the initial effectiveness of oncogene-directed cancer therapeutics, acquired drug resistance remains the ultimate "Achilles' heel" for long-term durable remission in cancer patients. Acquisition of drug resistance is not more evident elsewhere than in the use of tyrosine kinase inhibitors, imatinib and dasatinib, for patients with chronic myelogenous leukemia. Hence, even though imatinib initially produces remission in the chronic phase, ultimately these therapeutics fail via the emergence of drug resistance, in which chronic myelogenous leukemia could inevitably progress to a terminal blast phase culminating in fatal outcome. Technically, it is challenging to predict the onset of drug resistance in a small number of oncogene-transformed cells, making the decision of when and how to employ second-generation tyrosine kinase inhibitors, or employ novel compounds that would be of benefit in treating drug-resistant Bcr-Abl mutants mainly retrospective. Here, we characterize a rapid and sensitive real-time fluorescent resonance energy transfer-based assay that is able to detect the in vivo activity of Bcr-Abl and its inhibition by small molecule compounds. Due to its real-time and in vivo nature, such an approach has the potential to monitor a drug-resistant phenotype, as well as to identify pharmaceutical agents that inhibit drug-resistant Bcr-Abl oncoproteins in vivo.