The use of FDG-PET to target tumors by radiotherapy.

Fluorodeoxyglucose positron emission tomography (FDG-PET) plays an increasingly important role in radiotherapy, beyond staging and selection of patients. Especially for non-small cell lung cancer, FDG-PET has, in the majority of the patients, led to the safe decrease of radiotherapy volumes, enabling radiation dose escalation and, experimentally, redistribution of radiation doses within the tumor. In limited-disease small cell lung cancer, the role of FDG-PET is emerging. For primary brain tumors, PET based on amino acid tracers is currently the best choice, including high-grade glioma. This is especially true for low-grade gliomas, where most data are available for the use of (11)C-MET (methionine) in radiation treatment planning. For esophageal cancer, the main advantage of FDG-PET is the detection of otherwise unrecognized lymph node metastases. In Hodgkin's disease, FDG-PET is essential for involved-node irradiation and leads to decreased irradiation volumes while also decreasing geographic miss. FDG-PET's major role in the treatment of cervical cancer with radiation lies in the detection of para-aortic nodes that can be encompassed in radiation fields. Besides for staging purposes, FDG-PET is not recommended for routine radiotherapy delineation purposes. It should be emphasized that using PET is only safe when adhering to strictly standardized protocols.

Use of skin markers and electronic portal imaging to improve verification of tangential breast irradiation.

We investigated the added value of skin markers in 566 electronic portal images (EPIs) in 48 breast cancer patients treated with tangential fields. EPIs were matched to the corresponding DRRs using skin markers, anatomy, or a combination of both. Skin markers improved determination of setup errors in cranio-caudal direction.

Continuing risk of ipsilateral breast relapse after breast-conserving therapy at long-term follow-up.

PURPOSE: Currently, the local treatment of most patients with early invasive breast cancer consists of breast-conserving therapy (BCT). We have previously reported on the risk factors for ipsilateral breast relapse (IBR) in 1,026 patients treated with BCT after a median follow-up of 5.5 years. In the present study, we evaluated the IBR incidence and the risk factors for IBR after prolonged follow-up. METHODS AND MATERIALS: We updated the disease outcome for all 1,026 patients using the clinical information collected from the medical registration of The Netherlands Cancer Institute and performed step-wise proportional hazard Cox regression analysis to identify the risk factors associated with an increased risk of IBR after BCT at long-term follow-up. RESULTS: After a median follow-up of 13.3 years, 114 patients had developed an IBR as the first event. The IBR rate was 9.3% and 13.8%, respectively, at 10 and 15 years. Also, the increase in IBR was continuous without reaching a plateau, even after 15 years. Univariate analysis showed that involved surgical resection margins, young age, vascular invasion, and the presence and quantity of an in situ component are risk factors for IBR. Multivariate analysis showed that tumor-positive surgical resection margins (hazard ratio, 2.9; 95% confidence interval, 1.7-5.2, p = 0.0002) or the presence of vascular invasion (hazard ratio, 2.0; 95% confidence interval, 1.2-3.2, p = 0.004) is the major independent risk factor for IBR. CONCLUSIONS: The data from long-term follow-up showed a constant increase in IBR among patients treated by BCT, even after 15 years, without reaching a plateau. Involved surgical resection margins and vascular invasion were the most important risk factors for IBR.

Evaluation of three different CT simulation and planning procedures for the preoperative irradiation of operable rectal cancer.

PURPOSE: To find the best procedure regarding quality and work load for treatment planning in operable non-locally advanced rectal cancer using 3D CT-based information. METHODS: The study population consisted of 62 patients with non-locally advanced tumours, as defined by MRI in the lower (N=16), middle (N=25) and upper (N=21) rectum referred for preoperative short-course radiotherapy. In procedure 1 (Pr1), planning in one central plane was performed (field borders/shielding based on bony anatomy). In procedure 2 (Pr2), field borders were determined by 2 markers for the extension of the CTV in the cranial and ventral direction. Dose optimization was performed in one central and two border planes. In procedure 3(Pr3) the PTV volume (CTV was contoured on CT) received conformal treatment (3D dose optimization). RESULTS: Conformity index reached 1.6 for Pr3 vs. 2.2 for Pr2 (p<0.001). PTV coverage was 87%, 94%, 99% in Pr1, Pr2, Pr3, respectively (p=0.001). In Pr2 target coverage was below 95% for low/middle tumours. PTV coverage was reduced by narrow field borders (18-23%) and shielding (28%). A total of 43.5% (1-100) of the bladder volume was treated in Pr2 in contrast to 16% (0-68) in Pr3 (p<0.001). The maximum dose was exceeded in 10 patients (26-298 cc) and 2 patients (21-36 cc) in procedures 1 and 2, respectively. The overall time spent by technologists was 86 min for Pr3 vs 17 min in Pr2 and Pr1 (p<0.001), for radiation oncologists this difference was 24 vs 4 min (p<0.001). CONCLUSIONS: Pr1 does not fulfill todays quality requirements. Pr3 provides the best quality at the cost of working time. Pr2 is less time consuming, however, the PTV coverage was insufficient, with also much larger treatment volumes. An optimization of the PTV coverage in Pr2 even further enlarged the treatment volume.

18FDG-PET based radiation planning of mediastinal lymph nodes in limited disease small cell lung cancer changes radiotherapy fields: a planning study.

BACKGROUND AND PURPOSE: To investigate the influence of selective irradiation of 18FDG-PET positive mediastinal nodes on radiation fields and normal tissue exposure in limited disease small cell lung cancer (LD-SCLC). MATERIAL AND METHODS: Twenty-one patients with LD-SCLC, of whom both CT and PET images were available, were studied. For each patient, two three-dimensional conformal treatment plans were made with selective irradiation of involved lymph nodes, based on CT and on PET, respectively. Changes in treatment plans as well as dosimetric factors associated with lung and esophageal toxicity were analyzed and compared. RESULTS: FDG-PET information changed the treatment field in 5 patients (24%). In 3 patients, this was due to a decrease and in 2 patients to an increase in the number of involved nodal areas. However, there were no significant differences in gross tumor volume (GTV), lung, and esophageal parameters between CT- and PET-based plans. CONCLUSIONS: Incorporating FDG-PET information in radiotherapy planning for patients with LD-SCLC changed the treatment plan in 24% of patients compared to CT. Both increases and decreases of the GTV were observed, theoretically leading to the avoidance of geographical miss or a decrease of radiation exposure of normal tissues, respectively. Based on these findings, a phase II trial, evaluating PET-scan based selective nodal irradiation, is ongoing in our department.

Cardiotoxic effects of tangential breast irradiation in early breast cancer patients: the role of irradiated heart volume.

PURPOSE: To assess the risk of cardiovascular disease (CVD) after postlumpectomy irradiation restricted to tangential fields. METHODS AND MATERIALS: We assessed the incidence of CVD in 1601 patients with T1-2N0 breast cancer (BC) treated with breast tangentials in five different hospitals between 1980 and 1993. Patients treated with radiation fields other than breast tangentials and those treated with adjuvant chemotherapy were excluded. For patients with left-sided BC, maximum heart distance (MHD) was measured on the simulator films as a proxy for irradiated heart volume. Risk of CVD by laterality and MHD categories was evaluated by Cox proportional hazards regression analysis. RESULTS: Follow-up was complete for 94% of the patients, and median follow-up was 16 years. The incidence of CVD overall was 14.1%, of ischemic heart disease 7.3%, and for other types of heart disease 9.2%, with a median time to event of 10 to 11 years. The incidence of CVD was 11.6% in patients with right-sided BC, compared with 16.0% in left-sided cases. The hazard ratio associated with left-sided vs. right-sided BC was 1.38 (95% confidence interval [CI], 1.05-1.81) for CVD overall, 1.35 (95% CI, 0.93-1.98) for ischemic heart disease , and 1.53 (95% CI, 1.09-2.15) for other heart disease, adjusted for age, diabetes, and history of CVD. The risk of CVD did not significantly increase with increasing MHD. CONCLUSIONS: Patients irradiated for left-sided BC with tangential fields have a higher incidence of CVD compared with those with right-sided cancer. However, the risk does not seem to increase with larger irradiated heart volumes.

Prone breast irradiation for pendulous breasts.

The purpose of this study was to quantify the differences in doses in the organs at risk and to compare the PTV coverage and dose homogeneity of patients with pendulous breasts between prone and supine position. In 10 patients a CT-based treatment plan was made in prone and supine position. Data about dose homogeneity and doses to organs at risk were collected. Dose homogeneity turned out to be better in prone position and doses in organs at risk were lower, but with the current technique, this occurred at the cost of a reduced PTV coverage.

Set-up verification and 2-dimensional electronic portal imaging device dosimetry during breath hold compared with free breathing in breast cancer radiation therapy.

PURPOSE: To compare set-up and 2-dimensional (2D) electronic portal imaging device (EPID) dosimetry data of breast cancer patients treated during voluntary moderately deep inspiration breath hold (vmDIBH) and free breathing (FB). METHODS AND MATERIALS: Set-up data were analyzed for 29 and 51 consecutively treated patients, irradiated during FB and vmDIBH, respectively. Of the 51 vmDIBH patients, the first 25 had undergone an extra trained computed tomography (CT) scan and used an additional "breathing stick" (vmDIBH_trained). The last 26 patients did not use the breathing stick and did not undergo a trained CT (vmDIBH_untrained). The delivered 2D transit dose was measured with EPID in 15 FB and 28 vmDIBH patients and compared with a 2D predicted dose by calculating global gamma values γ using 5% and 5 mm as dose difference and distance-to-agreement criteria, respectively. Measurements with a percentage of pixels with an absolute gamma value > 1 (|γ| > 1) greater than 10% were classified as deviating. RESULTS: Only small, sub-millimeter differences were seen in the set-up data between the different patient groups. The mean of means, systematic error, and random error ranged from - 0.6 mm to 3.3 mm. The percentage of pixels with |γ| > 1 for all patients was 9.8% (2-25.8). No statistically significant differences were observed between the patient groups. In total, 38% of the gamma images were classified as deviating: 43.6% in vmDIBH_untrained patients compared with 38.0% in vmDIBH_trained patients and 33.3% in FB patients (P > .05). CONCLUSION: Both set-up and 2D EPID dosimetry data indicate that reproducibility of radiation therapy for patients treated during FB and vmDIBH is similar. Small but not significant differences in 2D EPID dosimetry were observed. Further investigation with 3-dimensional EPID dosimetry is recommended to investigate the clinical relevance of deviant gamma images.

Quality assurance of axillary radiotherapy in the EORTC AMAROS trial 10981/22023: the dummy run.

PURPOSE: To assess and if needed improve the compliance of participating institutions to the radiotherapy guidelines of the EORTC AMAROS trial 10981/22023 comparing axillary radiotherapy to axillary surgery in sentinel node positive patients with early stage breast cancer. MATERIALS AND METHODS: A transverse contour and a frontal view radiograph of the axillary region of a 'dummy' patient were sent to all institutions intending to participate in the trial with the request to produce a radiotherapy treatment plan according to the protocol guidelines. Additional information on dose prescription, the treatment technique and field matching with breast fields and internal mammary lymph node fields was requested in a questionnaire. RESULTS: Eighteen institutions have performed the dummy run. At first assessment, the dose was not specified according to the protocol in seven cases, while two institutions did not comply with the dose prescription of 50 Gy in 25 fractions. Dose heterogeneity was over 20% in 10 institutions, caused by the use of a two-field technique in eight cases. Ten institutions did not apply special techniques to obtain non-overlapping match planes. In 10 cases, one or more field borders or blocks were positioned incorrectly. Following recommendations from the quality assurance committee given to the participating institutions on an individual basis, 10 institutions adapted their technique. Thereafter, 16 institutions could be accepted for trial participation. CONCLUSIONS: A number of potential protocol deviations were found at first assessment. Since recommendations led to a large number of adaptations by the participants, a considerable improvement in protocol compliance and inter-institutional consistency was achieved.

A comparison in cosmetic outcome between per-operative interstitial breast implants and delayed interstitial breast implants after external beam radiotherapy.

BACKGROUND AND PURPOSE: Interstitial implants for brachytherapy boost in the breast conserving therapy of breast cancer can be performed in two ways; implants during the tumor excision (per-operative implants) or after the external beam therapy (delayed interstitial implants). Differences in cosmetic outcome were investigated. PATIENTS AND METHODS: Cosmetic results in 47 patients having a per-operative implant were compared to 123 patients having a delayed interstitial implant in a matched case-control study. Cosmesis was scored on a four-point-scale varying from 0 (excellent) to 3 (poor). RESULTS: After mean follow-up of 63 months, three observers found no difference in cosmetic outcome between the two groups after adjustment for variables found to be related with cosmesis (difference in mean score 0.50, P=0.26). Implant volume at 100% isodose was not found to differ (P=0.084) between the per-operative group (mean 102 cm3, S.D. 34 cm3) and the delayed group (mean 93 cm3, S.D. 29 cm3). CONCLUSIONS: Performing per-operative implants has not led to smaller implants. The method of performing brachytherapy does not result in marked differences in cosmetic outcome.

Rapid decline of follicular lymphoma-associated chylothorax after low dose radiotherapy to retroperitoneal lymphoma localization.

Chylothorax is caused by disruption or obstruction of the thoracic duct or its tributaries that results in the leakage of chyle into the pleural space. A number of interventions have been used to treat chylothorax including the treatment of the underlying disease. Lymphoma is found in 70% of cases with nontraumatic malignant aetiology. Although patients usually have advanced lymphoma, supradiaphragmatic disease is not always present. We discuss the case of a 63-year-old woman presenting with progressive respiratory symptoms due to chylothorax. She was diagnosed with a stage IIE retroperitoneal grade 1 follicular lymphoma extending from the coeliac trunk towards the pelvic inlet. Despite thoracocentesis and medium-chain triglycerides (MCT), diet chylothorax reoccurred. After low dose radiotherapy (2 × 2 Gy) to the abdominal lymphoma there was a marked decrease in lymphadenopathy at the coeliac trunk and a complete regression of the pleural fluid. In this case, radiotherapy was shown to be an effective nontoxic treatment option for lymphoma-associated chylothorax with long-term remission of pleural effusion.

Long-term survival of stage T4N0-1 and single station IIIA-N2 NSCLC patients treated with definitive chemo-radiotherapy using individualised isotoxic accelerated radiotherapy (INDAR).

BACKGROUND: Non-small cell lung cancer (NSCLC) stage T4N0-1 or single nodal station IIIA-N2 are two stage III sub-groups for which the outcome of non-surgical therapy is not well known. We investigated the results of individualised isotoxic accelerated radiotherapy (INDAR) and chemotherapy in this setting. METHODS: Analysis of NSCLC patients included in 2 prospective trials (NCT00573040 and NCT00572325) stage T4N0-1 or IIIA-N2 with 1 pathologic nodal station, treated with chemo-radiotherapy (CRT) using INDAR with concurrent or sequential platinum-based chemotherapy. Overall survival (OS) was updated and calculated from date of diagnosis (Kaplan-Meier). Toxicity was scored following CTCAEv3.0. To allow comparison with other articles the subgroups were also analysed separately for toxicity, progression free and overall survival. RESULTS: 83 patients (42 T4N0-1 and 41 IIIA-N2) were identified: the median radiotherapy dose was 65Gy. Thirty-seven percent of patients received sequential CRT and 63% received concurrent CRT. At a median follow-up of 48 months the median OS for T4N0-1 patients was 34 months with 55% 2-year survival and 25% 5-year survival. For stage IIIA-N2 at a median follow-up of 50 months the median OS was 26 months with 2- and 5-year survival rates of 53% and 24%, respectively. CONCLUSION: Chemo-radiation using INDAR yields promising survival results in patients with single-station stage IIIA-N2 or T4N0-1 NSCLC.

A prospective study comparing the predictions of doctors versus models for treatment outcome of lung cancer patients: a step toward individualized care and shared decision making.

BACKGROUND: Decision Support Systems, based on statistical prediction models, have the potential to change the way medicine is being practiced, but their application is currently hampered by the astonishing lack of impact studies. Showing the theoretical benefit of using these models could stimulate conductance of such studies. In addition, it would pave the way for developing more advanced models, based on genomics, proteomics and imaging information, to further improve the performance of the models. PURPOSE: In this prospective single-center study, previously developed and validated statistical models were used to predict the two-year survival (2yrS), dyspnea (DPN), and dysphagia (DPH) outcomes for lung cancer patients treated with chemo radiation. These predictions were compared to probabilities provided by doctors and guideline-based recommendations currently used. We hypothesized that model predictions would significantly outperform predictions from doctors. MATERIALS AND METHODS: Experienced radiation oncologists (ROs) predicted all outcomes at two timepoints: (1) after the first consultation of the patient, and (2) after the radiation treatment plan was made. Differences in the performances of doctors and models were assessed using Area Under the Curve (AUC) analysis. RESULTS: A total number of 155 patients were included. At timepoint #1 the differences in AUCs between the ROs and the models were 0.15, 0.17, and 0.20 (for 2yrS, DPN, and DPH, respectively), with p-values of 0.02, 0.07, and 0.03. Comparable differences at timepoint #2 were not statistically significant due to the limited number of patients. Comparison to guideline-based recommendations also favored the models. CONCLUSION: The models substantially outperformed ROs' predictions and guideline-based recommendations currently used in clinical practice. Identification of risk groups on the basis of the models facilitates individualized treatment, and should be further investigated in clinical impact studies.

Total gross tumor volume is an independent prognostic factor in patients treated with selective nodal irradiation for stage I to III small cell lung cancer.

PURPOSE: In non-small cell lung cancer, gross tumor volume (GTV) influences survival more than other risk factors. This could also apply to small cell lung cancer. METHODS AND MATERIALS: Analysis of our prospective database with stage I to III SCLC patients referred for concurrent chemo radiation therapy. Standard treatment was 45 Gy in 1.5-Gy fractions twice daily concurrently with carboplatin-etoposide, followed by prophylactic cranial irradiation (PCI) in case of non-progression. Only fluorodeoxyglucose (FDG)-positron emission tomography (PET)-positive or pathologically proven nodal sites were included in the target volume. Total GTV consisted of post chemotherapy tumor volume and pre chemotherapy nodal volume. Survival was calculated from diagnosis (Kaplan-Meier ). RESULTS: A total of 119 patients were included between May 2004 and June 2009. Median total GTV was 93 ± 152 cc (7.5-895 cc). Isolated elective nodal failure occurred in 2 patients (1.7%). Median follow-up was 38 months, median overall survival 20 months (95% confidence interval = 17.8-22.1 months), and 2-year survival 38.4%. In multivariate analysis, only total GTV (P=.026) and performance status (P=.016) significantly influenced survival. CONCLUSIONS: In this series of stage I to III small cell lung cancer patients treated with FDG-PET-based selective nodal irradiation total GTV is an independent risk factor for survival.

Forward intensity-modulated radiotherapy planning in breast cancer to improve dose homogeneity: feasibility of class solutions.

PURPOSE: To explore forward planning methods for breast cancer treatment to obtain homogeneous dose distributions (using International Commission on Radiation Units and Measurements criteria) within normal tissue constraints and to determine the feasibility of class solutions. METHODS AND MATERIALS: Treatment plans were optimized in a stepwise procedure for 60 patients referred for postlumpectomy irradiation using strict dose constraints: planning target volume (PTV)(95%) of >99%; V(107%) of <1.8 cc; heart V(5 Gy) of <10% and V(10 Gy) of <5%; and mean lung dose of <7 Gy. Treatment planning started with classic tangential beams. Optimization was done by adding a maximum of four segments before adding beams, in a second step. A breath-hold technique was used for heart sparing if necessary. RESULTS: Dose constraints were met for all 60 patients. The classic tangential beam setup was not sufficient for any of the patients; in one-third of patients, additional segments were required (<3), and in two-thirds of patients, additional beams (<2) were required. Logistic regression analyses revealed central breast diameter (CD) and central lung distance as independent predictors for transition from additional segments to additional beams, with a CD cut-off point at 23.6 cm. CONCLUSIONS: Treatment plans fulfilling strict dose homogeneity criteria and normal tissue constraints could be obtained for all patients by stepwise dose intensity modification using limited numbers of segments and additional beams. In patients with a CD of >23.6 cm, additional beams were always required.

Mature results of a phase II trial on individualised accelerated radiotherapy based on normal tissue constraints in concurrent chemo-radiation for stage III non-small cell lung cancer.

BACKGROUND: Sequential chemotherapy and individualised accelerated radiotherapy (INDAR) has been shown to be effective in non-small cell lung cancer (NSCLC), allowing delivering of high biological doses. We therefore performed a phase II trial (clinicaltrials.gov; NCT00572325) investigating the same strategy in concurrent chemo-radiation in stage III NSCLC. METHODS: 137 stage III patients fit for concurrent chemo-radiation (PS 0-2; FEV(1) and DLCO ≥ 30%) were included from April 2006 till December 2009. An individualised prescribed dose based on normal tissue dose constraints was applied: mean lung dose (MLD) 19 Gy, spinal cord 54 Gy, brachial plexus 66 Gy, central structures 74 Gy. A total dose between 51 and 69 Gy was delivered in 1.5 Gy BID up to 45 Gy, followed by 2 Gy QD. Radiotherapy was started at the 2nd or 3rd course of chemotherapy. Primary end-point was overall survival (OS) and secondary end-point toxicity common terminology criteria for adverse events v3.0 (CTCAEv3.0). FINDINGS: The median tumour volume was 76.4 ± 94.1 cc; 49.6% of patients had N2 and 32.1% N3 disease. The median dose was 65.0 ± 6.0 Gy delivered in 35 ± 5.7 days. Six patients (4.4%) did not complete radiotherapy. With a median follow-up of 30.9 months, the median OS was 25.0 months (2-year OS 52.4%). Severe acute toxicity (≥ G3, 35.8%) consisted mainly of G3 dysphagia during radiotherapy (25.5%). Severe late toxicity (≥ G3) was observed in 10 patients (7.3%). INTERPRETATION: INDAR in concurrent chemo-radiation based on normal tissue constraints is feasible, even in patients with large tumour volumes and multi-level N2-3 disease, with acceptable severe late toxicity and promising 2-year survival.

Individualised isotoxic accelerated radiotherapy and chemotherapy are associated with improved long-term survival of patients with stage III NSCLC: a prospective population-based study.

BACKGROUND: Individualised, isotoxic, accelerated radiotherapy (INDAR) allows the delivery of high biological radiation doses, but the long-term survival associated with this approach is unknown. METHODS: Patients with stage III NSCLC in the Netherlands Cancer Registry/Limburg from January 1, 2002 to December 31, 2008 were included. RESULTS: Patients (1002) with stage III NSCLC were diagnosed, of which 938 had T4 and/or N2-N3 disease. Patients treated with curative intent were staged with FDG-PET scans and a contrast-enhanced CT or an MRI of the brain. There were no shifts over time in the patient or tumour characteristics at diagnosis. The number of stage III NSCLC patients remained stable over time, but the proportion treated with palliative intent decreased from 47% in 2002 to 37% in 2008, and the percentage treated with chemo-radiation (RT) increased from 24.6% in 2002 to 47.8% in 2008 (p<0.001). The proportion of surgical patients remained below 5%. Sequential chemotherapy and conventional RT resulted in a median and a 5-year survival of 17.5 months and 8.4%, respectively, whereas with sequential chemotherapy and INDAR this was 23.6 months and 31%, respectively (p<0.001). Concurrent chemotherapy and INDAR was associated with a median and 2-year survival that was not reached and 66.7%, respectively (p=0.004). CONCLUSIONS: The proportion of patients treated with a curative intention with chemo-RT has increased markedly over time of observation. INDAR is associated with longer survival when compared to standard dose RT alone given with or without chemotherapy.

Is contrast enhancement required to visualize a known breast tumor in a pre-operative CT scan?

BACKGROUND AND PURPOSE: A pre-operative CT scan with contrast enhancement (CE) has recently been proposed to improve tumorbed delineation in breast conserving therapy. However, it is not clear whether CE is required for visualization of a known breast tumor. The main aims of this study were to compare the sensitivity of a CE-CT scan with a native CT scan (i.e. without CE) and to identify characteristics predictive for the requirement of CE. PATIENTS AND METHODS: Both a CE-CT and a native CT were made in 58 breast cancer patients (age 37-75 yr), prior to breast conserving surgery. Visibility of the tumor on CT was scored by three observers (clearly visible/doubtful/not visible). Age, tumor size, palpable tumor yes/no, histology, and visibility on mammography were analyzed with respect to the visibility of the tumor on the native CT. RESULTS: The sensitivity for tumor detection was better for CE-CT (95%) than for native CT (83%) (p<0.001). Only mammographic visibility scores appeared to be significantly correlated with the visibility of the tumor on the native CT (p=0.013). CONCLUSION: In most patients CE is not required to visualize a known breast tumor. Mammographic visibility is a good parameter to decide on the use of CE.

Treatment with curative intent of stage III non-small cell lung cancer patients of 75 years: a prospective population-based study.

BACKGROUND: There is little data on the survival of elderly patients with stage III non-small cell lung cancer (NSCLC). METHODS: Patients with stage III NSCLC in the Netherlands Cancer Registry/Limburg from January 1, 2002 to December 31, 2008 were included. FINDINGS: One thousand and two patients with stage III were diagnosed, of which 237 were 75 years or older. From 228 patients, co-morbidity scores were available. Only 33/237 patients (14.5%) had no co-morbidities, 195 (85.5%) had one or more important co-morbidities, 60 (26.3%) two or more co-morbidities, 18 (7.9%) three or more co-morbidities and 2 patients (0.9%) suffered from four co-morbidities. Forty-eight percent were treated with curative intent. No significant difference in Charlson co-morbidity, age or gender was found between patients receiving curative or palliative intent treatment. Treatment with curative intent was associated with increased overall survival (OS) compared to palliative treatment: median OS 14.2 months (9.6-18.7) versus 5.2 months (4.3-6.0), 2-year OS 35.5% versus 12.1%, for curative versus palliative treatment. FINDINGS: Patients who received only radiotherapy with curative intent had a median OS of 11.1 months (95% confidence interval [95% CI] 6.4-15.8) and a 5-year OS of 20.3%; for sequential chemotherapy and radiotherapy, the median OS was 18.0 months (95% CI 12.2-23.7), with a 5-year OS of 14.9%. Only four patients received concurrent chemo-radiation. INTERPRETATION: In this prospective series treating elderly patients with stage III NSCLC with curative intent was associated with significant 5-year survival rates.

Mature results of an individualized radiation dose prescription study based on normal tissue constraints in stages I to III non-small-cell lung cancer.

PURPOSE: We previously showed that individualized radiation dose escalation based on normal tissue constraints would allow safe administration of high radiation doses with low complication rate. Here, we report the mature results of a prospective, single-arm study that used this individualized tolerable dose approach. PATIENTS AND METHODS: In total, 166 patients with stage III or medically inoperable stage I to II non-small-cell lung cancer, WHO performance status 0 to 2, a forced expiratory volume at 1 second and diffusing capacity of lungs for carbon monoxide >or= 30% were included. Patients were irradiated using an individualized prescribed total tumor dose (TTD) based on normal tissue dose constraints (mean lung dose, 19 Gy; maximal spinal cord dose, 54 Gy) up to a maximal TTD of 79.2 Gy in 1.8 Gy fractions twice daily. Only sequential chemoradiation was administered. The primary end point was overall survival (OS), and the secondary end point was toxicity according to Common Terminology Criteria of Adverse Events (CTCAE) v3.0. RESULTS: The median prescribed TTD was 64.8 Gy (standard deviation, +/- 11.4 Gy) delivered in 25 +/- 5.8 days. With a median follow-up of 31.6 months, the median OS was 21.0 months with a 1-year OS of 68.7% and a 2-year OS of 45.0%. Multivariable analysis showed that only a large gross tumor volume significantly decreased OS (P < .001). Both acute (grade 3, 21.1%; grade 4, 2.4%) and late toxicity (grade 3, 4.2%; grade 4, 1.8%) were acceptable. CONCLUSION: Individualized prescribed radical radiotherapy based on normal tissue constraints with sequential chemoradiation shows survival rates that come close to results of concurrent chemoradiation schedules, with acceptable acute and late toxicity. A prospective randomized study is warranted to further investigate its efficacy.