Gy Of Thoracic Radiotherapy Research Articles

P-641 Concurrent 70 gy thoracic radiotherapy with weekly docetaxel orpaclitaxel after induction chemotherapy in patients with locally advanced non-small-cell lung cancer: Tolerance and efficacy from a non-randomized study

P-641 Concurrent 70 gy thoracic radiotherapy with weekly docetaxel orpaclitaxel after induction chemotherapy in patients with locally advanced non-small-cell lung cancer: Tolerance and efficacy from a non-randomized study

Compartmental responses after thoracic irradiation of mice: Strain differences

To examine and compare the molecular and cellular processes leading to radiation fibrosis and pneumonitis in C57BL/6J and C3H/HeN mice. At indicated times after various doses of thoracic irradiation, the cell populations obtained by bronchoalveolar lavage of C57BL/6J mice were differentially analyzed by cytology and assessed by RNase protection (RPA) assay for levels of cytokines and related genes. The molecular responses in bronchial alveolar lavage (BAL) populations were compared with those in whole lung of C57BL/6J mice and with those of C3H/HeN mice. The former strain develops late radiation fibrosis, whereas the latter develop subacute radiation pneumonitis. In C57BL/6J mice, a decrease in the total number of BAL cells was found 1 week after 6, 12, or 20 Gy thoracic irradiation with a subsequent dose-dependent increase up to 6 months. After 12 and 20 Gy, large, foamy macrophages and multinucleated cells became evident in BAL at 3 weeks, only to disappear at 4 months and reappear at 6 months. This biphasic response was mirrored by changes expression of mRNA for proinflammatory cytokines and the Mac-1 macrophage-associated antigen. As with BAL, whole lung tissue also showed biphasic cytokine and Mac-1 mRNA responses, but there were striking temporal differences between the two compartments, with changes in whole lung tissue correlating better than BAL with the onset of fibrosis in this strain. The radiation-induced proinflammatory mRNA responses had strain-dependent and strain-independent components. Thoracic irradiation of C3H/HeN induced similar increases in tumor necrosis factor (TNF)-alpha, interleukin (IL)-1alpha/beta, and interferon (IFN)-gamma mRNA expression in lung as it did in C57BL/6J mice during the "presymptom" phase at 1-2 months. However, immediately preceding and during the pneumonitic time period at 3-4 months, TNF-alpha and IL-1alpha/beta mRNAs were highly upregulated in C3H/HeN mice, which develop pneumonitis, but not in C57BL/6J mice, which do not. At the onset of radiation fibrosis in C57BL/6J mice (5-6 months), irradiated lungs had increased levels of IL-1alpha/beta and IFN-gamma mRNA expression, but the TNF-alpha response was, notably, still muted. The major molecular and cellular events in lungs of C57BL/6J and C3H/HeN mice, which develop late fibrosis and subacute pneumonitis after thoracic irradiation respectively, take place within the interstitium and are not reflected within BAL populations. The initial proinflammatory responses are similar in the two strains, but later responses reflect the latent time to lesion development. TNF-alpha expression at 3-4 months may be important in radiation-induced pneumonitis, and its downregulation is important in avoiding this radiation-induced complication.

In regard to Bogart et al.: 70 Gy thoracic radiotherapy is feasible concurrent with chemotherapy for limited-stage non–small-cell lung cancer: Analysis of cancer and leukemia group B study 39808 (Int J Radiat Oncol Biol Phys 2004;59:460–468)

In regard to Bogart et al.: 70 Gy thoracic radiotherapy is feasible concurrent with chemotherapy for limited-stage non–small-cell lung cancer: Analysis of cancer and leukemia group B study 39808 (Int J Radiat Oncol Biol Phys 2004;59:460–468)

649 Update on the toxicity and response of a phase I trial of concurrent, daily gefitinib and radiation or chemo-radiation for patients with locally advanced squamous cell cancer of the head and neck (LASCCHN)

This dose-escalation study was performed to determine the recommended phase II dose of oral capecitabine to be delivered concurrently with thoracic radiation therapy and weekly docetaxel in patients with locally advanced esophageal carcinoma.Patients with operable stage II or III esophageal carcinoma were staged by endoscopic ultrasonography and computed tomography. Two cycles of docetaxel (80 mg/m2) and carboplatin (target area under the concentration-time curve: 6 mg/ml × min) were delivered over 6 weeks. This was followed by concurrent weekly docetaxel (15 mg/m2), thoracic radiotherapy (50.4 Gy in 28 fractions), and increasing doses of capecitabine (500–3500 mg) given before each fraction of radiotherapy. After restaging, responding patients continued to esophagectomy within 4 to 8 weeks of completing chemoradiotherapy.Forty-four patients were enrolled, and 40 were assessable for the dose-ranging component of concurrent chemoradiotherapy. Endoscopic ultrasonography stages at enrollment were T3N1 (29 patients), T3N0 (4 patients), T2N1 (6 patients), and T4N0 (one patient). The maximum tolerated dose of capecitabine was 3500 mg. Thirty-six patients had surgery; 83% had R0 resection, and 17% had pathological complete response. Median overall survival was 23.5 months, with 34 and 27% alive at 3 and 5 years.The recommended phase II dose of capecitabine is 3500 mg when given concurrently with 50.4 Gy of thoracic radiotherapy in 28 fractions and weekly docetaxel. This trimodality therapy for operable locally advanced esophageal carcinoma was very well tolerated and remarkably active. This regimen holds promise for the treatment of esophageal carcinoma and warrants further investigation.

70 Gy thoracic radiotherapy is feasible concurrent with chemotherapy for limited-stage small-cell lung cancer: analysis of Cancer and Leukemia Group B study 39808

Purpose To prospectively evaluate the feasibility of delivering 70 Gy once-daily thoracic radiotherapy (TRT), concurrent with chemotherapy, in the treatment of limited-stage small-cell lung cancer (L-SCLC). Materials and methods Eligible patients received two cycles of induction paclitaxel (175 mg/m 2 on Day 1) and topotecan (1 mg/m 2 on Days 1–5) with granulocyte colony stimulating factor support, followed by three cycles of carboplatin (area under the curve = 5 on Day 1) and etoposide (100 mg/m 2 on Days 1–3). TRT (70 Gy, 2 Gy/fx/7 weeks) was initiated with the first cycle of carboplatin and etoposide. Prophylactic cranial irradiation was offered to patients achieving a complete response or good partial response. Results Ninety percent of patients (57 of 63) proceeded to protocol TRT. There was one treatment-related fatality. Nonhematologic Grade 3/4 toxicities affecting more than 10% of patients, during or after TRT, were dysphagia (16%/5%) and febrile neutropenia (12%/4%). The response rate to all therapy was 92% and the median overall survival is 22.4 months (95% confidence interval 16.1, ∞). Twenty-eight patients remain alive with a median follow-up of 24.7 months. Conclusion 70 Gy once-daily TRT can be delivered safely in the cooperative group setting for patients with L-SCLC. Initial efficacy data are encouraging. The hypothesis that high-dose once-daily TRT results in comparable or improved survival compared with twice-daily accelerated TRT warrants testing in a Phase III trial.

Randomized trial of chemoradiotherapy to 61 Gy [no S] versus chemoradiotherapy to 45 Gy followed by surgery [S] using cisplatin etoposide in stage IIIa non-small cell lung cancer (NSCLC): intergroup trial 0139, RTOG (9309)

Purpose/Objective: Optimal treatment for IIIa, N2 positive NSCLC needs definition from large randomized trials. Small phase III trials support the use of chemotherapy followed by [S]. Increasingly concurrent chemoradiotherapy produces substantial 2- and 3-year survival. SWOG 8805, a large phase II study employing cisplatin [P] etoposide [E] and 45 Gy thoracic radiotherapy (TRT) followed by resection demonstrated that patients achieving nodal complete response (CR) survived quite well. Intergroup 0139 tested the hypothesis that PE + concurrent 61 Gy TRT may be adequate, but [S] following induction therapy might either improve survival or increase morbidity/mortality. Study endpoints are progression free, median and overall survival, as well as pattern of failure.

70 Gy thoracic radiotherapy (TRT) is feasible concurrent with chemotherapy for limited stage small cell lung cancer (L-SCLC): preliminary analysis of a CALGB phase II trial

70 Gy thoracic radiotherapy (TRT) is feasible concurrent with chemotherapy for limited stage small cell lung cancer (L-SCLC): preliminary analysis of a CALGB phase II trial

Apoptosis and Bcl-2 Expression in Irradiated Lungs and the Effect of Pentoxifylline

We measured number of bcl-2, apoptotic, neutrophil, and surfactant apoprotein D (SP-D) positive cells in irradiated rat lungs during different time points after the sublethal whole-thorax irradiation of rats. We also investigated the influence of pentoxifylline (PTX) therapy on these markers. Wistar rats were given 15 Gy thoracic irradiation and PTX (35 mg/kg) twice a week. Animals were examined histologically and imunohistochemically at intervals from 1-12 weeks. In non-treated rats compared with treated rats, bcl-2 expression was significantly inhibited from 4 weeks after irradiation. A higher apoptosis presence in non-treated rats from 4 weeks was found and apoptosis development in PTX-treated animals was delayed and started 8 weeks after irradiation. Similar differences were measured during neutrophil granulocytes examination. Neutrophil penetration in non-treated rats was found 5 weeks after irradiation in contrast to the RP onset of PTX-treated animals 8 weeks after irradiation. The number of SP-D positive cells in non-treated rats observed until 5 weeks after irradiation was higher than in the control group. PTX-treated animals expressed higher number of SP-D positive cells during the whole experiment than the control group. We suggest that apoptosis is linked to neutrophil granulocyte actions during the RP onset and that PTX-therapy causes diminished inflammation development.

The Alveolar Septal Thickness and Type II Pneumocytes Number in Irradiated Lungs, Time Expression and the Effect of Pentoxifylline

We studied the relationship between type II pneumocytes number and alveolar septal thickness during different time after sublethal whole-thorax irradiation of rats and we investigated the influence of pentoxifylline (TNF-alpha inhibitor). Wistar rats were exposed to 15 Gy thoracic irradiation and pentoxifylline (35 mg/kg) twice a week. Lungs were examined histologically and immunohistochemically at intervals ranging from 1-12 weeks and alveolar septal thickness, number of type II pneumocytes (identified by immunoreactivity for cytokeratin 18), and neutrophile granulocytes were counted. Significant increase of alveolar septal thickness and type II pneumocytes depletion 3 weeks after irradiation were found. Correlation of these markers was r = -0.759. Pentoxifylline significantly inhibits increased alveolar septal thickness without the influence on type II pneumocytes number. Neutrophil penetration started 5 weeks after irradiation in non-treated animals, 8 weeks after irradiation in PTX-treated rats. We suggest that pneumocytes depletion is linked to increased vascular permeability, and pentoxifylline therapy does not influence on pneumocytes kinetics after irradiation.

Safe pulmonary resection after chemotherapy and high-dose thoracic radiation

Background. Pulmonary resection after high-dose thoracic irradiation is reported to be associated with a high morbidity and mortality, and has been considered to be prohibitive. Methods. We report safe pulmonary resection in 19 consecutive patients receiving neoadjuvant therapy that included greater than 59 Gy thoracic radiation. The mean thoracic radiation dose was 61.8 Gy (range 59.5–66.5) and mean age was 52 years (range 36–72 years). Cell type was adenocarcinoma (6), squamous (7), and other non-small cell lung cancer (NSCLC) (6). Sixteen of 19 patients received concurrent chemotherapy. Median time from end of treatment to surgical resection was 89 days (range 22–258 days). Surgical resection included 13 lobectomies and six pneumonectomies (four right, two left). Results. A complete pathologic response was seen in 8 of 19 (42%) patients. Three patients required intraoperative transfusion of blood. Mean intensive care unit stay was 2.0 days (range 1–8 days), and mean length of stay (LOS) was 8.0 days (range 3–18 days). There were four postoperative complications; one bronchopulmonary fistula, one subarachnoid-pleural fistula, and 2 patients with prolonged atelectasis. There was no incidence of acute respiratory distress syndrome (ARDS) or operative mortality. Conclusions. Pulmonary resection, including pneumonectomy, after chemotherapy and high-dose thoracic radiation may be performed safely with a low rate of intraoperative and postoperative complications.

Induction of lung tumors in C3H strain mice after single or fractionated irradiation with X-rays.

Murine model for lung tumor induction was studied in C3H/He male mice, a strain with low spontaneous incidence of lung tumors. Dose-response relationships in lung tumor induction were compared following irradiation with single doses and split doses of X-rays to the thorax either at night or in the daytime. The tumor incidence after a single 1.25 Gy dose at night during the period of nocturnal activity almost reached the maximum level after a 5 Gy dose in the daytime. Proliferative activity determined by observing the labeling index with tritiated thymidine in the normal lung was low as a whole, but tended to decrease in the daytime. When the proliferative response was induced by X-irradiation, significantly higher activity was observed at night. These circadian fluctuations were thought to affect radiosensitivity and lung tumor induction in mice. When split doses or fractionated doses of X-rays were applied to the thorax, lung tumor incidence definitely increased. The incidence after two 7.5 Gy doses with a 12 hr-interval was 41%, 3-fold higher than that after a single 15 Gy dose. Moreover, fractionated whole body irradiations (three times at 3 Gy with 3-month-interval) after a single 7.5 Gy thoracic irradiation was most effective in increasing not only the incidence (47%) but also the multiplicity of the lung tumor. More than 30% of tumor-bearing mice had two or more tumors following thoracic and whole body irradiations, while only 10% of tumor-bearers had multiple tumors after single or fractionated thoracic irradiation alone.