Background Radiation pneumonitis is a dose-limiting toxicity for patients undergoing concurrent chemoradiation therapy (CCRT) for non-small cell lung cancer (NSCLC). We performed an individual patient data meta-analysis to determine factors predictive of clinically significant pneumonitis. Methods After a systematic review of the literature, data was obtained on 836 patients who underwent CCRT in Europe, North America and Asia. Patients were randomly divided into training and validation sets (2/3 vs. 1/3 of patients). Factors predictive of symptomatic pneumonitis (grade ≥ 2 by one of several scoring systems) or fatal pneumonitis were evaluated using logistic regression. Recursive partitioning analysis (RPA) was used to define risk groups. Results The median radiotherapy dose was 60 Gy, and median follow-up was 2.3 years. Most patients received concurrent cisplatin/etoposide (38%) or carboplatin/paclitaxel (26%). The overall rate of symptomatic pneumonitis was 29.8% (n=249), with fatal pneumonitis in 1.9% (n=16). In the training set, factors predictive of symptomatic pneumonitis were lung volume receiving ≥20 Gy (V20) [OR:1.03 per 1% increase, p=0.008], and carboplatin/paclitaxel chemotherapy [OR:3.33, p<0.001], with a trend for age [OR: 1.24 per decade, p=0.09]; the model remained predictive in the validation set with good discrimination in both datasets (c-statistic>0.65). On RPA, the highest risk of pneumonitis (>50%) was in patients >65 years of age receiving carboplatin/paclitaxel. Predictors of fatal pneumonitis were daily dose >2 Gy, V20, and lower-lobe tumor location. Conclusions Several treatment-related risk factors predict the development of symptomatic pneumonitis, and elderly patients who undergo CCRT with carboplatin-paclitaxel chemotherapy are at highest risk. Fatal pneumonitis, although uncommon, is related to dosimetric factors and tumor location.

PurposeTo compare target dose distribution, comformality, normal tissue avoidance, and irradiated body volume (IBV) in 3DCRT using classic anatomical landmarks (c3DCRT), 3DCRT fitting the PTV (f3DCRT), and intensity-modulated radiation therapy (IMRT) in patients with locally advanced rectal cancer (LARC).Materials and methodsFifteen patients with LARC underwent c3DCRT, f3DCRT, and IMRT planning. Target definition followed the recommendations of the ICRU reports No. 50 and 62. OAR (SB and bladder) constraints were D5 ≤ 50 Gy and Dmax < 55 Gy. PTV dose prescription was defined as PTV95 ≥ 45 Gy and PTVmin ≥ 35 Gy. Target coverage was evaluated with the D95, Dmin, and Dmax. Target dose distribution and comformality was evaluated with the homogeneity indices (HI) and Conformity Index (CI). Normal tissue avoidance of OAR was evaluated with the D5 and V40. IBV at 5 Gy (V5), 10 Gy (V10), and 20 Gy (V20) were calculated.ResultsThe mean GTV95, CTV95, and PTV95 doses were significantly lower for IMRT plans. Target dose distribution was more inhomogeneous after IMRT planning and 3DCRTplans had significantly lower CI. The V40 and D5 values for OAR were significantly reduced in the IMRT plans .V5 was greater for IMRT than for f3DCRT planning (p < 0.05) and V20 was smaller for IMRT plans(p < 0.05).ConclusionsIMRT planning improves target conformity and decreases irradiation of the OAR at the expense of increased target heterogeneity. IMRT planning increases the IBV at 5 Gy or less but decreases the IBV at 20 Gy or more.

BackgroundInhibitor of DNA binding 1 (Id1) and 3 (Id3) genes have been related with the inhibition of cell differentiation, cell growth promotion and tumor metastasis. Recently, Id1 has been identified as an independent prognostic factor in patients with lung adenocarcinoma, regardless of the stage. Furthermore, Id1 may confer resistance to treatment (both, radiotherapy and chemotherapy).MethodsWe have studied, using monoclonal antibodies for immunohistochemistry, the Id1 and Id3 tumor epithelial expression in 17 patients with stage III-N2 non-small cell lung cancer (NSCLC) treated with definitive chemoradiotherapy.ResultsId1 expression is observed in 82.4% of the tumors, whereas Id3 expression is present in 41.2% of the samples. Interestingly, Id1 and Id3 expression are mutually correlated (R = 0.579, p = 0.015). In a subgroup analysis of patients with the most locally advanced disease (T4N2 stage), co-expression of Id1 and Id3 showed to be related with a worse overall survival (45 vs 6 months, p = 0.002). A trend towards significance for a worse progression free survival (30 vs 1 months, p = 0.219) and a lower response rate to the treatment (RR = 50% vs 87.5%, p = 0.07) were also observed.ConclusionsA correlation between Id1 and Id3 protein expression is observed. Id1 and Id3 co-expression seems associated with a poor clinical outcome in patients with locally advanced NSCLC treated with definitive chemoradiotherapy.

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Simultaneous chemoradiation is used in unresectable pancreatic cancer for palliation. It is not known if the use of adjuvant surgery will benefit this group of patients. From November 1991 to September 1998, 47 patients with unresectable pancreatic cancer were treated with simultaneous preoperative radiation therapy (45 Gy) and chemotherapy. Chemotherapy followed three different protocols: cisplatin, 5-fluorouracil +/- paclitaxel; cisplatin, 5-fluorouracil (protracted infusion); and docetaxel and gemcitabine. Whipple pancreatoduodenectomy was performed 1 month after the end of radiation in patients selected for resection. Twenty-three unresectable tumors after preoperative treatment (47%) received an additional dose (10-12 Gy) of radiotherapy using intraoperative or external radiation therapy. Twelve patients (26%) were considered to have clinically resectable tumors after the preoperative treatment. Nine patients had surgery (19% of the total number of patients), and 2 of them had complete pathologic response. After chemoradiation, two patients died of pneumonia and gastrointestinal bleeding, respectively, and another two patients died in the postoperative period. Local recurrence was observed in 22% of the patients and 57% had distant metastases. Three-year survival rates for patients with unresectable and resectable tumors was 0% (median survival 10 months) and 48% (median survival 23 months), respectively (p = 0.0004). Preoperative treatment with chemotherapy and radiotherapy in patients with unresectable pancreatic cancer is feasible. In some patients, the tumor can be resected, and in addition some cases of complete pathologic response were found. Long-term survivors were observed in the group of resected tumors. More effective chemotherapy regimens are needed because the majority of the patients died of metastatic disease.

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According to the published evidence as well as our own experience, SBRT is a safe and feasible approach for early NSCLC. Its results may be comparable with surgery treatment.