Results of a phase I dose‐escalation study using three‐dimensional conformal radiotherapy in the treatment of inoperable nonsmall cell lung carcinoma

Abstract

BACKGROUNDThe objective of this study was to report the results of a Phase I dose‐escalation study using three‐dimensional conformal radiation therapy (3D‐CRT) for the treatment of patients with nonsmall cell lung carcinoma (NSCLC).METHODSBetween 1991 and 2003, 104 patients were enrolled for 3D‐CRT at Memorial Sloan‐Kettering Cancer Center. The median patient age was 69 years. Twenty‐eight percent of patients had Stage I–II NSCLC, 33% of patients had Stage IIIA NSCLC, 32% of patients had Stage IIIB NSCLC, and 6% of patients had recurrent NSCLC. Induction chemotherapy was received by 16% of patients. Radiation was delivered in daily fractions of 1.8 grays (Gy) for doses ≤ 81.0 Gy and in daily fractions of 2.0 Gy for higher doses. Accrual at a dose level was complete when 10 patients received the intended dose without unacceptable acute morbidity.RESULTSAfter an incident of fatal acute radiation pneumonitis at the starting dose of 70.2 Gy, the protocol was modified to limit normal tissue complication probabilities (NTCP) to < 25%. The dose was then escalated from 70.2 Gy, to 75.6 Gy, 81.0 Gy, and 84.0 Gy, with at least 10 patients treated at each dose level. Unacceptable pulmonary toxicity occurred at 90.0 Gy. Subsequently, another 10 patients were accrued at the 84.0 Gy level with acceptable toxicity. Thus, 84.0 Gy was the maximum tolerated dose (MTD). The crude late pulmonary toxicity rate was 7%, the 2‐year local control rate was 52%, the disease‐free survival rate was 33%, and the overall survival rate was 40%. The median survival was 21.1 months. Overall survival was improved significantly in patients who received ≥ 80.0 Gy.CONCLUSIONSThe MTD of 3D‐CRT for NSCLC with an NTCP constraint of 25% was 84.0 Gy in the current study. There was a suggestion of improved survival in patients who received 80.0 Gy. Cancer 2005. © 2005 American Cancer Society.

Intensity-modulated radiation therapy (IMRT) for inoperable non-small cell lung cancer: The Memorial Sloan-Kettering Cancer Center (MSKCC) experience

“…Several studies from the University of Michigan, the Radiation Oncology Therapy Group (RTOG), and Memorial Sloan-Kettering Cancer Center (MSKCC) have shown the value of dose escalation to doses as high as 102.9 Gy in controlling locoregional recurrences in NSCLC. [4][5][6][7] However, even in these studies it was difficult to meaningfully escalate dose in patients with large tumors. The value of dose escalation was demonstrated in a study from MSKCC where Rengan et al reviewed the treatment of stage III tumors with large (≥ 100cc) gross tumor volumes (GTV) using 3D-CRT and found that a 10 Gy increase in dose correlated to a 36.4% decrease in local failure rates.…”

A new plan quality index for dose painting radiotherapy

“…Biologically related models, such as tumor control probability (TCP) and normal tissue complication probability (NTCP), have been widely used for evaluating the quality of RT plans 20 , 21 , 22 . In particular, several studies addressed TCP models for an inhomogeneously irradiated tumor 23 , 24 .…”

Toxicity report of a phase 1/2 dose‐escalation study in patients with inoperable, locally advanced nonsmall cell lung cancer with helical tomotherapy and concurrent chemotherapy

“…Only 1 patient with grade 5 toxicity was reported in those 3 studies combined. 26,27,37 However, those trials reported on patients with stage I, II, and III NSCLC; only 16% received induction chemotherapy, and no concurrent chemotherapy was allowed. However, the reported RTOG grade !3 late lung toxicity rate of 14% in DCs I, II, and III appeared to be acceptable.…”