J. McAleese

18F-FDG PET-CT SIMULATION FOR NON-SMALL-CELL LUNG CANCER: EFFECT IN PATIENTS ALREADY STAGED BY PET-CT

PURPOSE Positron emission tomography (PET), in addition to computed tomography (CT), has an effect in target volume definition for radical radiotherapy (RT) for non-small-cell lung cancer (NSCLC). In previously PET-CT staged patients with NSCLC, we assessed the effect of using an additional planning PET-CT scan for gross tumor volume (GTV) definition. METHODS AND MATERIALS A total of 28 patients with Stage IA-IIIB NSCLC were enrolled. All patients had undergone staging PET-CT to ensure suitability for radical RT. Of the 28 patients, 14 received induction chemotherapy. In place of a RT planning CT scan, patients underwent scanning on a PET-CT scanner. In a virtual planning study, four oncologists independently delineated the GTV on the CT scan alone and then on the PET-CT scan. Intraobserver and interobserver variability were assessed using the concordance index (CI), and the results were compared using the Wilcoxon signed ranks test. RESULTS PET-CT improved the CI between observers when defining the GTV using the PET-CT images compared with using CT alone for matched cases (median CI, 0.57 for CT and 0.64 for PET-CT, p = .032). The median of the mean percentage of volume change from GTV(CT) to GTV(FUSED) was -5.21% for the induction chemotherapy group and 18.88% for the RT-alone group. Using the Mann-Whitney U test, this was significantly different (p = .001). CONCLUSION PET-CT RT planning scan, in addition to a staging PET-CT scan, reduces interobserver variability in GTV definition for NSCLC. The GTV size with PET-CT compared with CT in the RT-alone group increased and was reduced in the induction chemotherapy group.

18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography–Based Radiotherapy Target Volume Definition in Non–Small-Cell Lung Cancer: Delineation by Radiation Oncologists vs. Joint Outlining With a PET Radiologist?

PURPOSE (18)F-Fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) has benefits in target volume (TV) definition in radiotherapy treatment planning (RTP) for non-small-cell lung cancer (NSCLC); however, an optimal protocol for TV delineation has not been determined. We investigate volumetric and positional variation in gross tumor volume (GTV) delineation using a planning PET/CT among three radiation oncologists and a PET radiologist. METHODS AND MATERIALS RTP PET/CT scans were performed on 28 NSCLC patients (Stage IA-IIIB) of which 14 patients received prior induction chemotherapy. Three radiation oncologists and one PET radiologist working with a fourth radiation oncologist independently delineated the GTV on CT alone (GTV(CT)) and on fused PET/CT images (GTV(PETCT)). The mean percentage volume change (PVC) between GTV(CT) and GTV(PETCT) for the radiation oncologists and the PVC between GTV(CT) and GTV(PETCT) for the PET radiologist were compared using the Wilcoxon signed-rank test. Concordance index (CI) was used to assess both positional and volume change between GTV(CT) and GTV(PETCT) in a single measurement. RESULTS For all patients, a significant difference in PVC from GTV(CT) to GTV(PETCT) exists between the radiation oncologist (median, 5.9%), and the PET radiologist (median, -0.4%, p = 0.001). However, no significant difference in median concordance index (comparing GTV(CT) and GTV(FUSED) for individual cases) was observed (PET radiologist = 0.73; radiation oncologists = 0.66; p = 0.088). CONCLUSIONS Percentage volume changes from GTV(CT) to GTV(PETCT) were lower for the PET radiologist than for the radiation oncologists, suggesting a lower impact of PET/CT in TV delineation for the PET radiologist than for the oncologists. Guidelines are needed to standardize the use of PET/CT for TV delineation in RTP.

Investigating the Potential Impact of Four-dimensional Computed Tomography (4DCT) on Toxicity, Outcomes and Dose Escalation for Radical Lung Cancer Radiotherapy

AIMS To investigate the potential dosimetric and clinical benefits predicted by using four-dimensional computed tomography (4DCT) compared with 3DCT in the planning of radical radiotherapy for non-small cell lung cancer. MATERIALS AND METHODS Twenty patients were planned using free breathing 4DCT then retrospectively delineated on three-dimensional helical scan sets (3DCT). Beam arrangement and total dose (55 Gy in 20 fractions) were matched for 3D and 4D plans. Plans were compared for differences in planning target volume (PTV) geometrics and normal tissue complication probability (NTCP) for organs at risk using dose volume histograms. Tumour control probability and NTCP were modelled using the Lyman-Kutcher-Burman (LKB) model. This was compared with a predictive clinical algorithm (Maastro), which is based on patient characteristics, including: age, performance status, smoking history, lung function, tumour staging and concomitant chemotherapy, to predict survival and toxicity outcomes. Potential therapeutic gains were investigated by applying isotoxic dose escalation to both plans using constraints for mean lung dose (18 Gy), oesophageal maximum (70 Gy) and spinal cord maximum (48 Gy). RESULTS 4DCT based plans had lower PTV volumes, a lower dose to organs at risk and lower predicted NTCP rates on LKB modelling (P < 0.006). The clinical algorithm showed no difference for predicted 2-year survival and dyspnoea rates between the groups, but did predict for lower oesophageal toxicity with 4DCT plans (P = 0.001). There was no correlation between LKB modelling and the clinical algorithm for lung toxicity or survival. Dose escalation was possible in 15/20 cases, with a mean increase in dose by a factor of 1.19 (10.45 Gy) using 4DCT compared with 3DCT plans. CONCLUSIONS 4DCT can theoretically improve therapeutic ratio and dose escalation based on dosimetric parameters and mathematical modelling. However, when individual characteristics are incorporated, this gain may be less evident in terms of survival and dyspnoea rates. 4DCT allows potential for isotoxic dose escalation, which may lead to improved local control and better overall survival.

Palmar fasciitis: a para-neoplastic phenomenon indicating recurrence of non small cell lung cancer – case report and review of the literature

Dear Editor, We report a case of a 74-year-old woman who developed a disabling, progressive thickening of the hands and feet with associated edema, 18 months into follow-up after having received radical radiotherapy for stage I NSCLC (non small cell lung cancer). While she had suffered from rheumatoid arthritis for over 30 years, it had been relatively indolent for a number of years and she was not on any disease-modifying drugs. The clinical features were felt to be more in keeping with palmar fasciitis as there was no swelling or pain within the joints but there was palpable thickening in the palmar fascia. Her proximal and distal interphalangeal (PIP and DIP) and metacarpophalangeal (MCP) joints were flexed with limitation of movements (Fig. 1). Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were within normal ranges. She also described a troublesome, dry cough and increased breathlessness. A computed tomography (CT) scan showed increasing hilar lymphadenopathy and follow-up CT/PET (fused CT/positron emission tomography scan) demonstrated local recurrence of her lung cancer. Systemic chemotherapy was felt to be of limited benefit due to her poor performance status but, because she was symptomatic, she was treated with re-irradiation to a dose of 20 Gy in five fractions. Two months later a CT/PET scan showed some shrinkage of disease (from 2.6 to 2 cm), and lowering of standardized uptake value (SUVmax: from 6.0 to 4.6) in keeping with response. She noted a significant improvement in her hands and feet immediately after radiotherapy finished with increasing range of movement, especially flexion of metacarpal-phalangeal joints. However, 6 weeks later she developed shortness of breath and a non-productive cough consistent with radiation pneumonitis. After starting prednisolone 40 mg her breathlessness resolved and she described further improvement with her palmar fasciitis, to the extent that she was now able to use both hands with minimal limitation. She has been maintained on lowdose steroids for the past year without deterioration of her fasciitis. Palmar fasciitis is a rare paraneoplastic phenomenon first described in 1982. Clinical manifestations include thickening of the palmar fascia and an inflammatory symmetrical arthritis commonly affecting knees, ankles, elbows and wrists. ‘‘Woody hands’’ is a term used to describe this condition. Differential diagnoses include reflex sympathetic dystrophy, scleroderma, Dupuytren’s contracture and eosinophilic fasciitis. Reflex sympathetic dystrophy usually affects one extremity only, is more slowly progressive and associated with vasomotor disturbance. The absence of Raynaud’s phenomenon, the lack of specific autoantibodies and the rapid progression of clinical features help exclude scleroderma and the indurated swelling of digits make Dupuytren’s disease an unlikely diagnosis. Eosinophilic fasciitis is associated with myalgia weight gain and a peripheral eosinophilia. In the case presented here, clinical features were distinct from the patient’s history of rheumatoid arthritis as there was no joint swelling or pain, but thickening of the palmar fascia causing considerable loss of function of the hands. Figure 1 Palmar thickening prior to radiotherapy. International Journal of Rheumatic Diseases 2012; 15: e8–e9

The Quality of Curative-intent Radiotherapy for Non-small Cell Lung Cancer in the UK.

AIMS Lung cancer is the leading cause of cancer-related death in the UK. The quality of curative-intent radiotherapy is associated with better outcomes. National quality standards from the National Institute for Health and Care Excellence (NICE) on patient work-up and treatment selection were used, with guidance from the Royal College of Radiologists on the technical delivery of radiotherapy, to assess the quality of curative-intent non-small cell lung cancer radiotherapy and to describe current UK practice. MATERIALS AND METHODS Radiotherapy departments completed one questionnaire for each patient started on curative-intent radiotherapy for 8 weeks in 2013. RESULTS Eighty-two per cent of centres returned a total of 317 proformas. Patient selection with positron emission tomography/computed tomography, performance status and Forced Expiratory Volume in 1 second (FEV1) was usually undertaken. Fifty-six per cent had pathological confirmation of mediastinal lymph nodes and 22% staging brain scans; 20% were treated with concurrent chemoradiation, 12% with Stereotactic Ablative Radiotherapy (SABR) and 8% with Continuous Hyperfractionated Accelerated Radiotherapy (CHART). Sixty-three per cent of patients received 55 Gy/20 fractions. Although respiratory compensation was routinely undertaken, only 33% used four-dimensional computed tomography. Seventy per cent of patients were verified with cone beam computed tomography. There was consistency of practice in dosimetric constraints for organs at risk and follow-up. CONCLUSIONS This audit has described current UK practice. The latest recommendations for patient selection with pathological confirmation of mediastinal lymph nodes, brain staging and respiratory function testing are not universally followed. Although there is evidence of increasing use of newer techniques such as four-dimensional computed tomography and cone beam image-guided radiotherapy, there is still variability in access. Efforts should be made to improve access to modern technologies and quality assurance of radiotherapy plans.

P3.16-18 Modern Radiotherapy Increases Patient Access to Curative Intent Radiotherapy in Non-Small Cell Lung Cancer

Background: The authors evaluated the efficacy, patterns of failure, toxicity and cost of body gamma-ray stereotactic ablative radiotherapy (Body Gamma-ray SABR) for patients with medically inoperable, clinical stage I/II non-small cell lung cancer (NSCLC) with 8 years of follow-up. Clinical staging was performed according to the sixth edition of the American Joint Committee on Cancer TNM staging system. Method: Eligible patients who had no previous treatments, with histologically confirmed NSCLC, determined as clinical stage I /II, underwent OUR-QGD type of the body gamma-ray SABR (70 grays in 10 fractions for gross target volume) at the Radiation Oncology Department, People’s Liberation Army Airforce General Hospital, Beijing, China from January 2007 to July 2010. All patients were immobilized by vacuum bag, and then a slow CT scan was performed without any respiration gating. The total radiation dose of 50%, 60%, and 70% isodose line were prescribed in 50, 60, and 70 Grey (Gy) correspondingly, covering 100% of the planning target volume (PTV), 90% of the clinical target volume (CTV), and 80% of the gross target volume (GTV) in 10 fractions. The CT scan and/or positron emission tomography/ computed tomography were every 3 months for the first 2 years, every 6 months for the next 3 years, and then annually thereafter to evaluate the efficacy of the treatment. The primary endpoint was overall survival. Result: A total of 29 patients were eligible for analysis. The median age of the patients was 71 years (55-87), and the median follow-up was 8.1 years (6.8-10.3). The 1-year, 3-year, 5-year and 8year overall survival rates were 93.1%, 72.1%, 59.4% and 44.8%, and the local, regional and distant disease recurrence were 10.3%, 13.8% and 13.8% at 5 years and 10.3%, 17.2% and 20.7% at 8 years. Two patients (6.9%) experienced grade 3 treatment-related adverse events. No patients developed grade 4 or 5 adverse events. The median cost of body gamma-ray SABR is 4838 dollars (4615-4923 dollars). Conclusion: With long-term follow-up, the results of the current study demonstrated outstanding local control and low toxicity after body gamma-ray SABR in patients with clinical stage I/II NSCLC. The dominant failure included regional and distant disease recurrence. And the body Gamma-ray SABR is pretty cost-effective.

Single institution, retrospective comparison of toxicity and outcome for static 5-field IMRT versus VMAT in the delivery of prostate and pelvic nodal irradiation in high-risk prostate cancer.

147 Background: There is emerging evidence for the role of pelvic nodal irradiation in high-risk prostate cancer. We have assessed the toxicity rates and outcomes with 2 different radiotherapy techniques. Methods: The baseline disease metrics, toxicity and outcome data for men treated at our institution with prostate and pelvic nodal irradiation during a 2 year period were retrospectively collected. The radiotherapy technique, either 5-field IMRT or VMAT was recorded along with a single dose-level to indicate normal tissue exposure (V50 to bowel and rectum, that is the percentage of total organ receiving ≥ 50Gy). Results: 67 men with a median age of 64 years were identified; 83.6% were Gleason ≥ 8, 82.1% were ≥ T3a, 50.7% were N1, 4.5% were M1a/M1b. All had neoadjuvant and concurrent hormone therapy. All received 74Gy to prostate; 70.1% received 60Gy to pelvic nodes, 28.4% received 55Gy to pelvic nodes (1 patient received 56Gy). 55.2% were treated with static IMRT and 44.8% with VMAT with no significant d...

Impact of 4-Dimensional CT (4D-CT) on Toxicity, Outcomes, and Dose Escalation for Radical Lung Cancer Radiation Therapy

of the histological types of non-SCLC, accounting for 1-3% of all SCLC. The low incidence has precluded the development of randomized clinical trials. To investigate the clinical features, prognostic factors, as well as the role of radiation therapy, we designed this retrospective analysis. Materials/Methods: Between January 2004 and December 2011, patients with histologically diagnosed CSCLC in CIH-CAMS were retrospectively analyzed. The overall survival (OS), progression free survival (PFS), locoregional recurrence free survival (LRFS), and distant metastasis survival (DMFS) were calculated by Kaplan-Meier method. Results: Forty-four patients were enrolled, with a median age of 59 years old. The most common combined component was squamous cell carcinoma (59.1%). The disease of stage I, II, III and IV was 13.6%, 20.5%, 47.7% and 18.2%, respectively. Thirty-seven patients (84.1%) received multimodality treatment, including 37 (84.1%) with chemotherapy, 34 (77.2%) with surgery, and 23 (52.3%) with radiation therapy. The median follow-up was 24 months. The median time of OS, PFS and LRFS was 26.5-, 13.3-, 18.4-month, respectively. The 1-, 3and 5-year OS was 68.6%, 46.9% and 32.8%, respectively, with corresponding PFS of 51%, 45.4% and 32.3%, and LRFS of 61.7%, 43.3% and 34.6%, respectively. The median DMFS of patients with stage I-III disease was 40.8 months, with 1-, 3and 5-year DMFS of 59.5%, 51.5% and 36.6%, respectively. On univariate analysis, KPS 3 cm (p Z 0.049), and positive margin (p Z 0.001) were associated with lower OS. Radiation therapy significantly improved OS in patients with IIIA/IIIB disease (p Z 0.032), positive lymph nodes (p Z 0.006), trended to increase the OS in patients with T3-4 disease (p Z 0.179), but not in those with different age, sex or tumor site. For patients who had received surgery, radiation therapy significantly improved OS only in patient with >4 metastatic lymph nodes (pZ 0.025). Conclusions: CSCLC is a rare type of SCLC with relative limited stage and good prognosis. KPS 3 cm and positive margin were poor prognostic factors. At present, multimodality therapy is recommended. Radiation therapy can benefit the patients with IIIA/IIIB CSCLC, or positive lymph nodes, or those with >4 metastatic lymph nodes after surgery. Author Disclosure: Y. Men: None. H. Zhouguang: None. L. Jun: None. L. Jima: None. Z. Zongmei: None. F. Qinfu: None. C. Dongfu: None. Z. Hongxing: None. X. Zefen: None. W. Luhua: None.

Induction chemotherapy in non-small cell lung cancer: experience at the Northern Ireland Cancer Centre

Introduction: Induction chemotherapy in Non Small Cell Lung Cancer (NSCLC) has shown a survival benefit in a recent metaanalysis and in randomised controlled trials (RCTs). At the Northern Ireland Cancer Centre we performed a retrospective audit to assess the outcomes of all patients with stage III NSCLC treated with induction chemotherapy between 2001 and 2005. Methods: All patients receiving radical treatment for NSCLC in the period 2001 to 2005 were identified using the regional surgical and oncology databases and records were screened to find patients with Stage III disease who had chemotherapy prior to surgery or radical radiotherapy. Demographic data was collected and actuarial survival estimated with Kaplan Meier methods. Results: In total 73 patients with Stage III NSCLC received induction chemotherapy. 37 patients had Stage IIIA disease and 14 of these were treated with surgery; radiological response to induction chemotherapy was demonstrated in 77%, the two year survival rate was 57%. In the 23 patients with stage IIIA disease who had radical radiotherapy, the radiological response rate was 60%, the 2 year survival 39%. In total 36 patients with stage IIIB NSCLC received induction chemotherapy, 16 proceeding to surgery and 20 to radical radiotherapy, with 2 year overall survival rates of 44% and 30% respectively. Conclusion: Radical surgery and radical radiotherapy are feasible following induction chemotherapy and have good results in our centre. Our surgical figures are particularly good viz a viz a recent RCT and require further scrutiny. Concurrent chemoradiotherapy may allow further improvements in survival.