What is the role of radiotherapy in malignant pleural mesothelioma?

OBJECTIVE: A review of the evidence supporting the use of radiotherapy in patients with mesothelioma was performed. METHODS: Relevant publications were searched for on Medline. RESULTS: In a Medline search on radiotherapy and mesothelioma, 611 hits were obtained. A limited number of prospective phase II trials of radiotherapy as part of trimodality protocols for early disease and in the palliation of pain were found, along with three small randomized controlled trials of port-site prophylaxis. CONCLUSION: No randomized data exist to support the use of radiotherapy after radical surgery, although there are a large number of publications describing its use as an integral part of therapy, including seven phase II studies. One ongoing trial is randomizing patients to radiotherapy or not after extrapleural pneumonectomy. None of these studies provided any assessment of radiotherapy independent of the other modalities investigated, nor did any formally assess intensity-modulated radiotherapy. There have been several reports of excessive toxicity with this technique, and its use should be limited to phase I studies until the basis of this toxicity is better understood. Three trials have looked at port-site prophylaxis, one supporting its use and two showing no evidence of benefit. Two studies addressed pain control prospectively, one showing definite but short-lived benefits. Implications. Radiotherapy is widely used in treating mesothelioma with little supporting evidence. More randomized trials are required to justify this use in all three common settings for its use.

Patient perceptions of their decision to undergo palliative chemotherapy in the Edinburgh Cancer Centre.

BACKGROUND: The decision to undergo chemotherapy for incurable cancer demands informed discussions about the risks and benefits of proposed treatments. Research has shown that many patients have a poor grasp of these factors. METHODS: An evaluation of the patient experience of palliative chemotherapy decision-making was undertaken. Patients with lung or gynaecological cancers were surveyed about their decision, what they understood about its risks and benefits, and how supported they felt. RESULTS: A total of 29 people with lung cancer (n = 21) or gynaecological cancer (n = 8) completed questionnaires. The majority felt sure about their decision, though many were less sure of the risks and benefits of treatment. Unprompted comments revealed significant nuance, including that the decision to undergo chemotherapy may not necessarily have felt like a choice. CONCLUSIONS: Our positive findings may reflect participant selection bias, or could represent genuine comfort in decision-making in Scottish oncology clinics. Further research is needed.

Increased but error-prone nonhomologous end joining in immortalized lymphoblastoid cell extracts from adult cancer patients with late radionecrosis.

PURPOSE: To study nonhomologous end joining in extracts of two lymphoblastoid cell lines derived from patients with late radionecrosis after radiotherapy. Both cell lines were previously shown to exhibit impaired rejoining of DNA double-strand breaks in a pulse-field gel electrophoresis assay. METHODS AND MATERIALS: We used a cell-free system and quantitative real-time polymerase chain reaction, as well as sequencing analysis of end joining products. RESULTS: Paradoxically, extracts of the two cell lines display increased rates of in vitro end joining of noncohesive termini compared with normal cell extracts. This increase was seen in the absence of added deoxyribonucleoside triphosphates and was sensitive to inhibition by wortmannin. Sequencing of the joined products revealed that, despite increased rates of end joining, the process was error prone with a greater frequency of deletions compared with that observed in normal controls. CONCLUSION: These findings are consistent with the suggestion that a promiscuous, deletion-prone abnormality of nonhomologous end joining might underpin the predisposition of certain radiotherapy patients to late radionecrosis. We hypothesize that some individuals might harbor subclinical defects in nonhomologous end joining that clinically manifest on challenge with high-dose radiation. Because both quantitative and qualitative aspects of end joining have demonstrably been influenced, we recommend that the study of patient samples should involve a combination of quantitative methods (e.g., quantitative real-time polymerase chain reaction), sequencing analysis, and a comparison of multiple join types.

International comparisons of survival from lung cancer: pitfalls and warnings.

Population-based survival data can provide valuable comparative data on outcome but should be interpreted with caution. Differences in data collection and analysis, patient and tumor characteristics and treatment options can have an impact on reported results. Ideally, data from the whole population, including clinical-only diagnoses, should be reported and the methods of case identification described. The relative survival rates should preferably be given. Data on patient characteristics such as age, sex, ethnicity and socioeconomic deprivation should be described, together with tumor details such as pathology and clinical stage. Whenever possible, details on the use of treatments should be reported.

Randomised trial of sequential versus concurrent chemo-radiotherapy in patients with inoperable non-small cell lung cancer (EORTC 08972-22973).

UNLABELLED: A randomised phase III study was performed comparing sequential (S) and concurrent (C) chemo-radiotherapy (CRT) in non-small cell lung cancer (NSCLC) patients. METHODS: One hundred and fifty-eight patients were randomised to receive two courses of Gemcitabine (1250mg/m(2) days 1, 8) and Cisplatin (75mg/m(2) day 2) prior to, or daily low-dose Cisplatin (6mg/m(2)) concurrent with radiotherapy, consisting of 24 fractions of 2.75Gy in 32 days, with a total dose of 66Gy. RESULTS: Acute haematological toxicity grade 3/4 was more pronounced in the sequential (S) (30% versus 6%), oesophagitis grade 3/4 more frequent in the concurrent (C) arm (5% versus 14%). Late oesophagitis grade 3 was 4% (S and C), pneumonitis grade 3/4 14% (S) and 18% (C). Because of the poor power of the study no significant differences in median survival (MS), overall survival (OS) and progression-free survival (PFS) could be detected. MS was 16.2 (S) and 16.5 (C) months, 2-year OS was 34% (S) and 39% (C), 3-year OS was 22% (S) and 34% (C). CONCLUSION: Radiotherapy 66Gy given concurrently with daily low-dose Cisplatin or after two courses of Gemcitabine/Cisplatin was well tolerated. Due to early closure no conclusions can be reached on the relative merits; both arms showed good OS.

Phase III study of matrix metalloproteinase inhibitor prinomastat in non-small-cell lung cancer.

PURPOSE: Matrix metalloproteinases (MMPs) degrade extracellular proteins and facilitate tumor growth, invasion, metastasis, and angiogenesis. This trial was undertaken to determine the effect of prinomastat, an inhibitor of selected MMPs, on the survival of patients with advanced non-small-cell lung cancer (NSCLC), when given in combination with gemcitabine-cisplatin chemotherapy. PATIENTS AND METHODS: Chemotherapy-naive patients were randomly assigned to receive prinomastat 15 mg or placebo twice daily orally continuously, in combination with gemcitabine 1,250 mg/m2 days 1 and 8 plus cisplatin 75 mg/m2 day 1, every 21 days for up to six cycles. The planned sample size was 420 patients. RESULTS: Study results at an interim analysis and lack of efficacy in another phase III trial prompted early closure of this study. There were 362 patients randomized (181 on prinomastat and 181 on placebo). One hundred thirty-four patients had stage IIIB disease with T4 primary tumor, 193 had stage IV disease, and 34 had recurrent disease (one enrolled patient was ineligible with stage IIIA disease). Overall response rates for the two treatment arms were similar (27% for prinomastat v 26% for placebo; P = .81). There was no difference in overall survival or time to progression; for prinomastat versus placebo patients, the median overall survival times were 11.5 versus 10.8 months (P = .82), 1-year survival rates were 43% v 38% (P = .45), and progression-free survival times were 6.1 v 5.5 months (P = .11), respectively. The toxicities of prinomastat were arthralgia, stiffness, and joint swelling. Treatment interruption was required in 38% of prinomastat patients and 12% of placebo patients. CONCLUSION: Prinomastat does not improve the outcome of chemotherapy in advanced NSCLC.

Randomized phase IIB trial of BLP25 liposome vaccine in stage IIIB and IV non-small-cell lung cancer.

PURPOSE: To evaluate the effect of BLP25 liposome vaccine (L-BLP25) on survival and toxicity in patients with stage IIIB and IV non-small-cell lung cancer (NSCLC). Secondary objectives included health-related quality of life (QOL) and immune responses elicited by L-BLP25. PATIENTS AND METHODS: Patients with an Eastern Cooperative Oncology Group performance status of 0 to 2 and stable or responding stage IIIB or IV NSCLC after any first-line chemotherapy were prestratified by stage and randomly assigned to either L-BLP25 plus best supportive care (BSC) or BSC alone. Patients in the L-BLP25 arm received a single intravenous dose of cyclophosphamide 300 mg/m2 followed by eight weekly subcutaneous immunizations with L-BLP25 (1,000 microg). Subsequent immunizations were administered at 6-week intervals. RESULTS: The survival results indicate a median survival time of 4.4 months longer for patients randomly assigned to the L-BLP25 arm (88 patients) compared with patients assigned to the BSC arm (83 patients; adjusted hazard ratio [HR] = 0.739; 95% CI, 0.509 to 1.073; P = .112). The greatest effect was observed in stage IIIB locoregional (LR) patients, for whom the median survival time for the L-BLP25 arm has not yet been reached compared with 13.3 months for the BSC arm (adjusted HR = 0.524; 95% CI, 0.261 to 1.052; P = .069). No significant toxicity was observed. QOL was maintained longer in patients on the L-BLP25 arm. CONCLUSION: L-BLP25 maintenance therapy in patients with advanced NSCLC is feasible with minimal toxicity. The survival difference of 4.4 months observed with the vaccine did not reach statistical significance. In the subgroup of patients with stage IIIB LR disease, a strong trend in 2-year survival in favor of L-BLP25 was observed.

Pemetrexed combined with oxaliplatin or carboplatin as first-line treatment in advanced non-small cell lung cancer: a multicenter, randomized, phase II trial.

PURPOSE: To determine efficacy and toxicity of two pemetrexed-based regimens in chemonaive patients with locally advanced or metastatic non-small cell lung cancer. EXPERIMENTAL DESIGN: Patients were randomly assigned to receive pemetrexed 500 mg/m(2) plus oxaliplatin 120 mg/m(2) (PemOx) or pemetrexed plus carboplatin AUC6 (PemCb). All drugs were given on day 1 of a 21-day cycle for up to six cycles. Folic acid and vitamin B(12) were given to all patients to minimize pemetrexed-related toxicities. RESULTS: Forty-one patients received PemOx and 39 received PemCb. Objective tumor response rates were 26.8% for PemOx patients (95% confidence interval, 14.2-42.9) and 31.6% for PemCb patients (95% confidence interval, 17.5-48.7). Median time to progression was 5.5 and 5.7 months, respectively, for PemOx and PemCb. Median overall survival times were 10.5 months for both treatment groups (range, <1 to >20 months). The 1-year survival rate was 49.9% for PemOx patients and 43.9% for PemCb patients. Common toxicity criteria grade 3 or 4 hematologic toxicities among PemOx patients were grade 3 or 4 neutropenia (7.3%), grade 3 thrombocytopenia (2.4%), and grade 3 anemia (2.4%). PemCb patients experienced grade 3 or 4 neutropenia (25.6%), grade 3 or 4 thrombocytopenia (17.9%), and grade 3 anemia (7.7%). Grade 3 vomiting occurred in three PemOx patients and grade 3 fatigue occurred in three PemCb patients. One grade 3 neurosensory toxicity occurred in the PemOx group. Three patients (PemOx 1 and PemCb 2) experienced febrile neutropenia. CONCLUSIONS: Efficacy measures for both regimens seem similar to the most effective chemotherapies for advanced non-small cell lung cancer (platinum combinations) with less hematologic and nonhematologic toxicity. Comparing either of these two regimens to platinum-based therapies in a large randomized trial is warranted.

Reduced DNA-dependent protein kinase activity in two cell lines derived from adult cancer patients with late radionecrosis.

Epstein-Barr virus-immortalized lymphoblastoid cell lines were derived from five patients with late radionecrosis. Two of these cell lines exhibited postradiation viability levels intermediate between normal cell lines and that from an individual with ataxia telangiectasia. Compared with controls, these two cell lines exhibited impaired ability to rejoin DNA double-strand breaks on pulsed-field gel electrophoresis and 6-10-fold reduced DNA-dependent protein kinase (DNA-PK) activity in vitro in cell-free extracts. Immunoblotting showed normal levels of Ku70, Ku80 and XRCC4 and the presence of DNA-PKcs in both cell lines. These findings suggest that DNA-PK might be an important factor affecting the predisposition of radiotherapy patients to late radionecrosis.

Intensity-modulated radiotherapy, not 3 dimensional conformal, is the preferred technique for treating locally advanced disease with high-dose radiotherapy: the argument against.

Intensity-modulated radiotherapy (IMRT) allows the delivery of high-dose radiotherapy to target volumes, while sparing adjacent normal tissues. This has been mooted as a method of treating larger and otherwise untreatable lung cancers or of escalating radiotherapy doses. The possibility of achieving these aims has been confirmed in many planning studies, but there is little supporting clinical data. No randomized trial has compared conformal and IMRT, few studies have reported the late outcomes of IMRT, and there is no evidence for improved control of lung cancer with increased radiation dose. Currently IMRT should be regarded as a promising but unproven experimental therapy in locally advanced non-small cell lung cancer. Searches of PubMed were performed looking for the terms "lung cancer and radiotherapy" and "lung cancer and intensity-modulated radiotherapy." The former was carried out for the period 2007, when the author last reviewed this topic, until 2014 and the latter from the first reference to this topic to the present. The first search produced 8000 and the second 929 hits. A standard hierarchy of evidence exists for interventions in medicine, ranging from systematic reviews of randomized trials to case-control studies and mechanism-based reasoning. The best evidence so far available for IMRT in stage III lung cancer is level 3 or 4 (low level evidence), and no currently accruing phase II or phase III trials are listed on the National Cancer Institute clinical trials website, although 1 study at the MD Anderson is open but not currently recruiting patients. This evidence will be reviewed. It would not be regarded as remotely adequate for the licensing of a new pharmacologic agent, and it does not seem unreasonable that the same standards of evidence for efficacy and safety should apply to the 2 branches of nonsurgical oncology.

The effect of overall treatment time on the survival and toxicity of radical radiotherapy for cervical carcinoma.

BACKGROUND AND PURPOSE: Overall treatment time is an important factor in the outcome of radical radiotherapy in head and neck, bladder and lung cancer and in cervix cancer treated over more than 7 weeks. This study analysed the effect of prolongation of overall treatment time on survival and late morbidity for patients receiving radical radiotherapy for cervical cancer treated with a 4-week regimen. MATERIALS AND METHODS: Using the departmental SAS data-base we identified all patients with cervix cancer treated between 1974 and 1988 and investigated the 647 patients who received 20 fractions of external beam radiotherapy plus intracavitary therapy with a total dose to point A of at least 60Gy. A retrospective case-note review identified tumour and treatment-related variables. RESULTS: Four hundred and twenty-five (66%) patients had at least one gap in treatment. Seventy-nine gaps (11%) were due to unavoidable patient or treatment-related causes. We could not find an effect of a treatment gap (P=0.43) or an increased overall treatment time (P=0.79) on the cause specific survival of patients. There was significantly more grade 4 morbidity in those patients treated over a short period (29-32 days) compared to the rest (P=0.005), possibly related to the loss of radiotherapy-free days to weekend intracavitary insertions. CONCLUSIONS: We could not demonstrate a significant effect of overall treatment time in this series of patients, almost all of whom were treated in less than 7 weeks. Those patients treated over the shortest period had an increased incidence of late morbidity.

Factors influencing the use of thoracic radiotherapy in lung cancer--an analysis of the 1995 Scottish lung cancer audit.

AIMS: To determine the frequency of delivery of thoracic radiotherapy (TRT) to patients with lung cancer in Scotland in 1995, and identify patient, disease and process variables affecting the probability of receiving TRT. METHODS: Retrospective case note audit of all patients with lung cancer diagnosed in Scotland in 1995. RESULTS: 1118 (30.8%) of 3,855 patients diagnosed with lung cancer in Scotland in 1995 for whom the medical records could be traced received TRT. In those who did not have small cell lung cancer, multivariate analysis indicated that diagnosis by a lung cancer specialist, clinical extent of disease and microscopic verification of cancer (all P<0.0001) and age (P=0.0005) were associated with an increased chance of receiving TRT. There was also a wide variation between different Health Boards (HB) of residence in the proportion of patients receiving TRT (P<0.0001). There was no association between the presence of local symptoms (cough, chest pain or haemoptysis) and the delivery of TRT. Of 351 patients with limited stage small cell lung cancer, 51 (14.5%) received chemotherapy and TRT, and 19 (5.4%) chemotherapy and cranial irradiation. CONCLUSIONS: TRT was delivered to fewer than one-third of patients with lung cancer in Scotland in 1995. This is lower than reported in other international audits. The chance of receiving TRT seemed to be associated with service issues rather than clinical need.

Phase II study of first-line bortezomib and cisplatin in malignant pleural mesothelioma and prospective validation of progression free survival rate as a primary end-point for mesothelioma clinical trials (European Organisation for Research and Treatment of Cancer 08052).

BACKGROUND: This was a prospective phase II study of cisplatin and bortezomib (CB) in the first line treatment of malignant pleural mesothelioma (MPM) with validation of progression free survival rate at 18 weeks (PFSR-18)(1) as primary end-point. METHODS: Chemotherapy-naïve patients with histologically proven MPM and performance status (PS) 0/1, were treated with cisplatin 75 mg/m(2) on day 1 and bortezomib 1.3mg/m(2) on days 1, 4, 8, 11 every 3 weeks. The primary end-point validation utilised the landmark method. RESULTS: Between 2007 and 2010 82 patients were entered. PFSR-18 was 53% (80% confidence intervals, CIs, 42-64%). The overall survival (OS) was 13.5 months (95% CI 10.5-15) with 56% (95% CI 44-66%) alive at 1 year. The median PFS was 5.1months (95% CI 3.3-6.5) and the response rate was 28.4% (95% CI 18.9-39.5%). The most frequent grade 3-4 toxicities were hyponatremia (46%), hypokalaemia (17%), fatigue (12.2%), thrombocytopenia (11%), neutropenia (9.7%) and neurotoxicity (motor, sensory, other: 1.2%, 8.5%, 2.4%). There were two toxic deaths (32 and 74days) due to acute pneumonitis and cardiac arrest. End-point validation showed that patients with no progression/progression at 18 weeks had median OS of 16.9/11.9 months, respectively. Hazard ratio was 0.46 (CI 0.32-0.67), logrank test and C-index were 0.007 and 0.60. CONCLUSION: The 50% PFSR-18 for CB was contained within the 80% CI for (42-64%). Therefore the null hypothesis could not be rejected. Accordingly this combination does not warrant further investigation. PFSR-18 was confirmed as a strong predictor of survival.

Emerging developments of chemoradiotherapy in stage III NSCLC.

Over the past decade, concomitant chemotherapy and radiotherapy has become the established treatment for patients with stage III non-small-cell lung cancer (NSCLC). Unfortunately, many patients with NSCLC are too old or have multiple comorbidities to withstand such aggressive treatments. Attempts to improve outcomes have included studies of radiotherapy dose escalation and new chemotherapy combinations, as well as adding biological agents and cancer vaccines to existing regimens. Technical radiotherapy modifications, including intensity-modulated radiotherapy and particle beam therapy, have also been investigated. Given the number of potential advances to current models of treatment development, phase III trials of any single new treatment can take years to complete, which is inadequate. To advance research within shorter timescales to improve patient outcomes, we need methods of improving clinical trial accrual, which might require changes in models of research governance, cooperative group activity, trial design and patient consent.

Radical radiotherapy with or without gemcitabine in patients with early stage medically inoperable non-small cell lung cancer.

BACKGROUND: Preclinical and phase I data suggest gemcitabine to be a potent radiosensitiser. This multicentre study addressed whether the addition of low dose gemcitabine to radical radiotherapy improved 2 year event-free survival in patients with medically inoperable stages I-II non-small cell lung cancer. AIM: To determine whether low dose gemcitabine increased event-free survival in patients with T1-2 N0-1 M0 NSCLC deemed unfit for surgery. METHODS: Patients with T1-2 N0-1 M0 NSCLC deemed unfit for surgery were randomised to 3D conformal radiotherapy delivering 55 Gy in 20 fractions over 4 weeks to known sites of cancer with (Arm B) or without (Arm A) 100mg/m(2) weekly gemcitabine. RESULTS: Study entry was terminated early because of slow accrual. 111 patients were randomised between March 2003 and December 2005, of whom 4 withdrew consent and 2 were lost to follow-up. Median age was 75 (range 49-88)years and 67 (63%) were male. 86 (81%) were PS 0-1 and 31 (30%) Charlson index 2 or greater. Event-free survival in arm A and B, respectively, was 42% and 46% at 2 years and 20% and 31% at 5 years (p=0.72), while overall survival was 56% and 52% at 2 years and 20% and 33% at 5 years (p=0.87). Two deaths from accelerated interstitial lung disease were seen in arm B, but toxicity was otherwise mild. CONCLUSION: No evidence of an improvement in event-free survival was seen with the addition of weekly gemcitabine at this dose for patients with early stage NSCLC unfit for surgery, although the power of the study was low.

Updated survival analysis in patients with stage IIIB or IV non-small-cell lung cancer receiving BLP25 liposome vaccine (L-BLP25): phase IIB randomized, multicenter, open-label trial.

PURPOSE: To present an updated survival analysis of an open-label, parallel-group, phase IIB trial of BLP25 liposome vaccine (L-BLP25) in patients with stage IIIB or IV non-small-cell lung cancer (NSCLC). METHODS: Patients were randomized to either L-BLP25 plus best supportive care (BSC) or BSC alone. Patients in the L-BLP25 arm received subcutaneous vaccinations of L-BLP25 930 µg weekly for 8 weeks, followed by maintenance vaccinations at 6-week intervals. RESULTS: Median survival time was 4.2 months longer in patients receiving L-BLP25 plus BSC (n = 88) than in those receiving BSC alone (n = 83; 17.2 months vs. 13.0 months, respectively; hazard ratio [HR] 0.745, 95% confidence interval [CI] 0.533-1.042). The 3-year survival rate was 31% in patients receiving L-BLP25 plus BSC and 17% in those receiving BSC (P = 0.035). In the stratified subset of patients with stage IIIB loco-regional (LR) disease, median survival time was 17.3 months longer in patients receiving L-BLP25 plus BSC (n = 35) than in those receiving BSC (n = 30; 30.6 months vs. 13.3 months, respectively; HR 0.548, 95% CI 0.301-0.999). In this subgroup, 3-year survival was 49% in patients receiving L-BLP25 plus BSC and 27% in those receiving BSC (P = 0.070). CONCLUSIONS: Confirming the initial results, further follow-up continues to show that survival time for patients with stage IIIB/IV NSCLC was longer with L-BLP25 plus BSC compared with BSC alone, with the greatest difference seen in patients with stage IIIB LR disease.

European Organisation for Research and Treatment of Cancer recommendations for planning and delivery of high-dose, high-precision radiotherapy for lung cancer.

PURPOSE: To derive recommendations for routine practice and clinical trials for techniques used in high-dose, high-precision thoracic radiotherapy for lung cancer. METHODS: A literature search was performed to identify published articles considered both clinically relevant and practical to use. Recommendations were categorized under the following headings: patient selection, patient positioning and immobilization, tumor motion, computed tomography and [18F]fluorodeoxyglucose-positron emission technology scanning, generating target volumes, radiotherapy treatment planning, treatment delivery, and scoring of response and toxicity. The American College of Chest Physicians grading of recommendations was used. RESULTS: Recommendations were identified for each of the recommendation categories. Although most of the recommended techniques have not been evaluated in multicenter clinical trials, their use in high-precision thoracic radiotherapy and stereotactic body radiotherapy (SBRT) appears to be justified on the basis of available evidence. CONCLUSION: Recommendations to facilitate the clinical implementation of high-precision conformal radiotherapy and SBRT for lung tumors were identified from the literature. Some techniques that are considered investigational at present were also highlighted.

Variations in target volume definition for postoperative radiotherapy in stage III non-small-cell lung cancer: analysis of an international contouring study.

PURPOSE: Postoperative radiotherapy (PORT) in patients with completely resected non-small-cell lung cancer with mediastinal involvement is controversial because of the failure of earlier trials to demonstrate a survival benefit. Improved techniques may reduce toxicity, but the treatment fields used in routine practice have not been well studied. We studied routine target volumes used by international experts and evaluated the impact of a contouring protocol developed for a new prospective study, the Lung Adjuvant Radiotherapy Trial (Lung ART). METHODS AND MATERIALS: Seventeen thoracic radiation oncologists were invited to contour their routine clinical target volumes (CTV) for 2 representative patients using a validated CD-ROM-based contouring program. Subsequently, the Lung ART study protocol was provided, and both cases were contoured again. Variations in target volumes and their dosimetric impact were analyzed. RESULTS: Routine CTVs were received for each case from 10 clinicians, whereas six provided both routine and protocol CTVs for each case. Routine CTVs varied up to threefold between clinicians, but use of the Lung ART protocol significantly decreased variations. Routine CTVs in a postlobectomy patient resulted in V(20) values ranging from 12.7% to 54.0%, and Lung ART protocol CTVs resulted in values of 20.6% to 29.2%. Similar results were seen for other toxicity parameters and in the postpneumectomy patient. With the exception of upper paratracheal nodes, protocol contouring improved coverage of the required nodal stations. CONCLUSION: Even among experts, significant interclinician variations are observed in PORT fields. Inasmuch as contouring variations can confound the interpretation of PORT results, mandatory quality assurance procedures have been incorporated into the current Lung ART study.