A Comparison of Two Stereotactic Body Radiation Fractionation Schedules for Medically Inoperable Stage I Non-small Cell Lung Cancer (original) (raw)
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2010
Purpose: To investigate therapeutic outcome of dose escalation ≥ 80 Gy in nonresected non-small cell lung cancer (NSCLC). Patients and Methods: 124 consecutive patients with histologically/cytologically proven NSCLC were enrolled. Tumor stage I, II, IIIA, and IIIB was diagnosed in 30, eight, 39, and 47 patients, respectively. 38 patients (31%) had weight loss > 5% during the 3 months before diagnosis. A median dose of 88.2 Gy (range 80.0-96.0 Gy), 69.3 Gy (63.0-88.0 Gy) and 56.7 Gy was applied to primary lesions, involved lymph nodes, and elective nodes (within a region of about 6 cm cranial to macroscopically involved nodes), respectively. Daily fractional ICRU doses of 2.0-2.2 Gy were delivered by the conformal target-splitting technique. 58 patients (47%) received induction chemotherapy, in median two cycles prior to radiotherapy. Results: Median follow-up time of all patients was 19 months, of patients alive 72.4 months (69-121 months). The cumulative actual overall survival rate at 2 and 5 years amounts to 39% and 11.3%, respectively, resulting in a median overall survival time of 19.6 months. According to stages I, II, IIIA, and IIIB, the median overall survival times are 31.8, 31.4, 19.0, and 14.5 months, respectively. The locoregional tumor control rate at 2 years is 49%. Apart from one treatment-related death (pneumonitis), acute toxicity according to EORTC/RTOG scores was moderate: lung grade 2 (n = 7), grade 3 (n = 3); esophagus grade 1 (n = 11); heart grade 3 (n = 1, pericarditis). No late toxicity grade > 1 has been observed. Conclusion: Sequential, conventionally fractionated high-dose radiotherapy by conformal target splitting is well tolerated. The results for survival and locoregional tumor control seem to at least equalize the outcome of simultaneous chemoradiation approaches, which, at present, are considered "state of the art" for patients with nonresected NSCLC. A higher potential of radiation therapy might be reached by accelerated fractionation regimens.
International Journal of Radiation Oncology*Biology*Physics, 1993
Purpose: A Phase I/II trial was conducted by the Radiation Therapy Oncology Group from 1984 to 1989 for 355 evaluable patients with non-small-cell lung cancer to assess tolerance to and efficacy of accelerated fractionation irradiation via concomitant boost. Methods and Materials: "Large" fields (primary tumor and locoregional lymph nodes) received 1.8 Gy followed after 4 to 6 hr by 1.8 Gy two to three times weekly to reduced "boost" fields (primary and involved nodes only). The total doses escalated during the study and started with 63 Gy in 5 weeks (45 Gy "large" field and 18 Gy "boost") for 61 patients. After follow-up for ongoing toxicity assessment, the total dose was increased to 70.2 Gy in 5.5 weeks (50.4 Gy "large" field and 19.8 Gy "boost") for the next 180 patients. The last 114 patients received 70.2 Gy in 5 weeks (45 Gy "large" field and 25.2 Gy "boost"). Results: Pretreatment patient characteristics were well balanced between the three treatment arms. Grade 3 acute toxicity was 7% for the 63 Gy arm; it was 14% and 17% for the two 70 Gy arms. Grade 4 or greater acute toxicities (esophagitis and pneumonitis) were 2 to 3% for all three arms. Late toxicities ranged between 5 and 9% (> Grade 3) and 0 to 2% (2 Grade 4), not statistically different among the three arms. There was no difference between the three regimens in median survival (9 months) or l-year survival (39 to 44%). However, the 2-year survivals ranged from 16% (63 Gy) to 21% ("shortened" 70.2 Gy). Among 176 patients who had the same criteria as Cancer and Leukemia Group B protocol 84-33 (American Joint Committee on Cancer Staging, 1984, Stage III; Karnofsky performance status 70 to 100; < 6% weight loss), the 2-year survival rates ranged from 18 to 22%. Conclusion: Concomitant boost accelerated fractionation irradiation regimens for non-small cell lung cancer may offer improved long-term survival without enhanced late toxicity. While acute toxicity is somewhat increased, further refinement of the relationship of "large" to "boost" field doses may improve the therapeutic ratio. Further Phase I/II testing seems justified and necessary, before concomitant boost accelerated fractionation irradiation is tested in Phase III trials for NSCLC. Non-small cell lung cancer, Accelerated fractionation irradiation, Concomitant boost irradiation.
Radiotherapy and Oncology, 2013
The optimal duration over which lung SBRT should be delivered is unknown. We conducted a randomized pilot study in patients treated with four fractions of lung SBRT delivered over 4 or over 11 days. Methods: Patients with a peripheral solitary lung tumor (NSCLC or pulmonary metastasis) 65 cm were eligible. For NSCLC lung tumors 63 cm, a dose of 48 Gy in 4 fractions was used, otherwise 52 Gy in 4 fractions was delivered. Patients were randomized to receive treatment over 4 consecutive days or over 11 days. The primary end-point was acute grade P2 toxicity. Secondary end-points included quality of life (QOL) assessed using the EORTC QLQ-C30 and QLQ-LC13 questionnaires. Results: Fifty four patients were enrolled. More patients in the 11 day group had respiratory symptoms at baseline. 55.6% patients treated over 4 days and 33.3% of patients treated over 11 days experienced acute grade P2 toxicity (p = 0.085). Dyspnea, fatigue and coughing domains were worse in the 11 day group at baseline. At 1 and 4 months, more patients in the 4 day group experienced a clinically meaningful worsening in the dyspnea QOL domain compared to the 11 day group (44.5% vs 15.4%, p = 0.02; 38.5% vs 12.0%, p = 0.03, respectively). However, raw QOL scores were not different at these time-points between treatment groups. Conclusions: Grade 2 or higher acute toxicity was more common in the 4 day group, approaching statistical significance. More patients treated on 4 consecutive days reported a clinically meaningful increase in dyspnea, although interpretation of these results is challenging due to baseline imbalance between treatment groups. Larger studies are required to validate these results. Ó 2013 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology 108 (2013) 320-325 Stereotactic body radiation therapy (SBRT) is an established treatment for early stage non-small cell lung cancer (NSCLC) and pulmonary metastases, providing excellent outcomes [1-5]. Despite widespread uptake, the optimum parameters for SBRT delivery remain undefined. Prospective studies comparing dosefractionation regimens are ongoing [6]. In the published literature, the duration over which lung SBRT has been delivered is diverse, with many centers separating each treatment fraction by several days, to ensure complete repair of sub-lethal damage occurs in normal tissues [2,3,7,8]. The standard in our cancer center has been to deliver 48-52 Gy in 4 fractions over 11 days. To date, no prospective study has compared different durations of treatment delivery of lung SBRT. As such, we conducted a randomized pilot study to compare two treatment schedules of lung SBRT. Methods This was a single institution, randomized, pilot study. Patients were randomly assigned, with a 1:1 ratio, to receive lung SBRT over 4 consecutive days or over 11 days. Eligibility criteria for participants Eligible participants were patients with peripheral stage I NSCLC or single pulmonary metastasis, 65 cm in diameter. Patients were required to be deemed medically inoperable or to have refused surgery. Patients were required to have a pathological diagnosis of malignancy in the lung, FDG-uptake on PET-CT, or evidence of clear tumor growth on serial CT scans. The attending
Acta Oncologica, 2006
We reviewed results of SBRT treatment of 138 patients with medically inoperable stage I NSCLC treated during 1996 Á 2003 at five different centres in Sweden and Denmark. Mean age was 74 years (range 56 Á90) with 69 men and 72 women. SBRT was delivered using a 3D conformal multifield technique and a stereotactic body frame. Doses delivered were 30 Á48 Gy (65% isodose at the periphery of planning target volume, PTV) in 2 Á4 fractions. Equivalent dose in 2 Gy fractions (EQD2) was in the range of 50 Á100 Gy. Mean gross tumour volume (GTV) was 39 cm 3 (2 Á436), and planning target volume was 101 cm 3 (11 Á719). Overall response rate (CR, PR) was 61% (84/138). SD was noted in 36% (50/138). During a median follow-up period of 33 months (1 Á107), 16 (12%) local failures occurred, ten of which also included distant metastases. Local failure was associated with tumour size, target definition and central or pleura proximity. Distant metastases occurred in 25% (35/138) of the patients. Ninety-one (65%) patients died during follow-up of which 55 patients (60%) died of other causes than lung cancer. Three-and 5-year overall survival was 52 and 26% respectively. Lung cancer specific 3-and 5-year overall survival was 66 and 40% respectively. Fifty nine percent (83/138) of the patients had no side effects. Fourteen patients experienced grade 3 Á4 toxicity according to radiation therapy oncology group (RTOG). EQD2 (/ v.s.B/55.6 Gy) showed a statistically significant benefit survival for the higher doses. SBRT for stage I NSCLC results in favourable local control not inferior to fractionated RT and with acceptable toxicity.
International Journal of Radiation Oncology*Biology*Physics, 2008
Purpose: To examine the effect of baseline forced expiratory volume in 1 second (FEV 1) and diffusion capacity for carbon monoxide (DL co) on posttreatment survival and pulmonary function decrease after stereotactic body radiotherapy (SBRT) for patients with early-stage non-small-cell lung cancer (NSCLC). Methods and Materials: Seventy medically inoperable patients with Stage I NSCLC were treated with definitive SBRT to a dose of 6,000 (Stage IA) or 6,600 cGy (Stage IB), given in three equal fractions. Baseline and serial posttreatment pulmonary function data were collected. Results: Median age was 70.5 years, and median follow-up was 2.17 years. Median pretreatment FEV 1 and DL co were 1.05 L and 10.06 mg/min/mm Hg, respectively. There was no significant decrease in survival in patients with baseline FEV 1 and DL co less than the median value and less than the lowest quartile, whereas patients with values greater than the highest quartile of baseline FEV 1 had significantly inferior survival. There was no significant effect of pretreatment FEV 1 or DL co on posttreatment levels. There was a statistically significant decrease in DL co of 1.11 mg/min/mm Hg/y. Conclusions: Poor baseline pulmonary function did not predict decreased survival or pulmonary function after treatment. A statistically significant decrease in DL co after treatment was seen, similar to decreases seen in studies delivering standard thoracic radiotherapy. We conclude that low pretreatment FEV 1 and/or DL co alone should not be used to exclude patients with NSCLC from treatment with SBRT.
Journal of Clinical Oncology, 2006
Purpose Surgical resection is standard therapy in stage I non–small-cell lung cancer (NSCLC); however, many patients are inoperable due to comorbid diseases. Building on a previously reported phase I trial, we carried out a prospective phase II trial using stereotactic body radiation therapy (SBRT) in this population. Patients and Methods Eligible patients included clinically staged T1 or T2 (≤ 7 cm), N0, M0, biopsy-confirmed NSCLC. All patients had comorbid medical problems that precluded lobectomy. SBRT treatment dose was 60 to 66 Gy total in three fractions during 1 to 2 weeks. Results All 70 patients enrolled completed therapy as planned and median follow-up was 17.5 months. The 3-month major response rate was 60%. Kaplan-Meier local control at 2 years was 95%. Altogether, 28 patients have died as a result of cancer (n = 5), treatment (n = 6), or comorbid illnesses (n = 17). Median overall survival was 32.6 months and 2-year overall survival was 54.7%. Grade 3 to 5 toxicity occu...
Journal of Thoracic Oncology, 2012
Introduction: To evaluate the influence of pretreatment pulmonary function (PF) on survival, early and late pulmonary toxicity after stereotactic body radiotherapy (SBRT) for early-stage non-small cell lung cancer. Methods: Four hundred eighty-three patients with 505 tumors of early-stage non-small cell lung cancer cT1-3 cN0 were treated with image-guided SBRT at five international institutions (1998-2010). Sixty-four percent of the tumors were biopsy-proven and 18Ffluorodeoxyglucose-positron emission tomography was performed for staging in 84%. Image-guided SBRT was performed with a median of three fractions to a median total dose of 54 Gy. Pretreatment PF was available for 423 patients, and 617 posttreatment PF tests from 270 patients were available. Results: A large variability of pretreatment PF was observed: the 90% range of forced expiratory volume in 1 second and diffusing capacity for carbon monoxide was 29 to 109% and 5.5 to 19.1 ml/min/mmHg, respectively. PF was significantly correlated with overall survival but not cause-specific survival: diffusing capacity for carbon monoxide of 11.2 ml/min/mmHg differentiated between 3-year overall survival of 66% and 42%. Radiation-induced pneumonitis grade ՆII occurred in 7% of patients and was not increased in patients with lower PF. A significant and progressive change of PF was observed after SBRT: PF decreased by 3.6% and 6.8% on average within 6 and 6 to 24 months after SBRT, respectively. Changes of PF after SBRT were significantly correlated with pre-treatment PF: PF improved for worst pretreatment PF and the largest loss was observed for best pretreatment PF. Conclusions: Image-guided SBRT is safe in terms of acute and chronic pulmonary toxicity even for patients with severe pulmonary comorbidities. SBRT should be considered as a curative treatment option for inoperable patients with pretreatment PF as reported in this study.