The impact of training and professional collaboration on the interobserver variation of lung cancer delineations: a multi-institutional study.

BACKGROUND: To assess the impact of training and interprofessional collaboration on the interobserver variation in the delineation of the lung gross tumor volume (GTVp) and lymph node (GTVln). MATERIAL AND METHODS: Eight target volume delineations courses were organized between 2008 and 2013. Specialists and trainees in radiation oncology were asked to delineate the GTVp and GTVln on four representative CT images of a patient diagnosed with lung cancer individually prior each course (baseline), together as group (interprofessional collaboration) and post-training. The mean delineated volume and local standard deviation (local SD) between the contours for each course group were calculated and compared with the expert delineations. RESULTS: A total 410 delineations were evaluated. The average local SD was lowest for the interprofessional collaboration (GTVp = 0.194 cm, GTVln = 0.371 cm) followed by the post-training (GTVp = 0.244 cm, GTVln = 0.607 cm) and baseline delineations (GTVp = 0.274 cm, GTVln: 0.718 cm). The mean delineated volume was smallest for the interprofessional (GTVp = 4.93 cm3, GTVln = 4.34 cm3) followed by the post-training (GTVp = 5.68 cm3, GTVln = 5.47 cm3) and baseline delineations (GTVp = 6.65 cm3, GTVln = 6.93 cm3). All delineations were larger than the expert for both GTVp and GTVln (p < .001). CONCLUSION: Our findings indicate that image interpretational differences can lead to large interobserver variation particularly when delineating the GTVln. Interprofessional collaboration was found to have the greatest impact on reducing interobserver variation in the delineation of the GTVln. This highlights the need to develop a clinical workflow so as to ensure that difficult cases are reviewed routinely by a second radiation oncologist or radiologist so as to minimize the risk of geographical tumor miss and unnecessary irradiation to normal tissue.

Primary tumour standardised uptake value is prognostic in nonsmall cell lung cancer: a multivariate pooled analysis of individual data.

(18)F-fluoro-2-deoxy-d-glucose positron emission tomography (PET) complements conventional imaging for diagnosing and staging lung cancer. Two literature-based meta-analyses suggest that maximum standardised uptake value (SUVmax) on PET has univariate prognostic value in nonsmall cell lung cancer (NSCLC). We analysed individual data pooled from 12 studies to assess the independent prognostic value of binary SUVmax for overall survival.After searching the published literature and identifying unpublished data, study coordinators were contacted and requested to provide data on individual patients. Cox regression models stratified for study were used.Data were collected for 1526 patients (median age 64 years, 60% male, 34% squamous cell carcinoma, 47% adenocarcinoma, 58% stage I-II). The combined univariate hazard ratio for SUVmax was 1.43 (95% CI 1.22-1.66) and nearly identical if the SUV threshold was calculated stratifying for histology. Multivariate analysis of patients with stage I-III disease identified age, stage, tumour size and receipt of surgery as independent prognostic factors; adding SUV (HR 1.58, 95% CI 1.27-1.96) improved the model significantly. The only detected interaction was between SUV and stage IV disease.SUV seems to have independent prognostic value in stage I-III NSCLC, for squamous cell carcinoma and for adenocarcinoma.

International radiation oncology trainee decision making in the management of radiotherapy-induced nausea and vomiting.

PURPOSE: This study explored international radiation oncology trainee decision making in the management of radiotherapy-induced nausea and vomiting (RINV). METHODS: Radiation oncology trainees who were members of the national radiation oncology associations of the USA, Canada, Netherlands, Australia, New Zealand, France, Spain and Singapore completed a Web-based survey. Respondents estimated the risks of nausea and vomiting associated with six standardised radiotherapy-only clinical case vignettes modelled after international anti-emetic guidelines and then committed to prophylactic, rescue or no therapy as an initial management approach for each case. RESULTS: One hundred and seventy-six trainees from 11 countries responded. Only 28 % were aware of any anti-emetic guideline. In general, risk estimates and management approaches for the high-risk and minimal risk cases varied less and were more in line with guideline standards than were estimates and approaches for the moderate- and low-risk cases. Prophylactic therapy was the most common approach for the high-risk and a moderate-risk case (83 and 71 % of respondents respectively), while rescue therapy was the most common approach for a second moderate-risk case (69 %), two low-risk cases (69 and 76 %) and a minimal risk case (68 %). A serotonin receptor antagonist was the most commonly recommended prophylactic agent. On multivariate analysis, a higher estimated risk of nausea predicted for recommending prophylactic therapy, and a lower estimated risk of nausea predicted for recommending rescue therapy. CONCLUSIONS: Radiation oncology trainee risk estimates and recommended management approaches for RINV clinical case vignettes varied and matched guideline standards more often for high-risk and minimal risk cases than for moderate- and low-risk cases. Risk estimates of nausea specifically were strong predictors of management decisions.

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.

Dexamethasone for the Prevention of a Pain Flare After Palliative Radiation Therapy for Painful Bone Metastases: The Multicenter Double-Blind Placebo-Controlled 3-Armed Randomized Dutch DEXA Study.

PURPOSE: After radiation therapy for painful bone metastases, up to 44% of patients report a pain flare (PF). Our study compared 2 dose schedules of dexamethasone versus placebo to prevent PF. METHODS AND MATERIALS: This double-blind, randomized, placebo-controlled trial allocated patients with painful bone metastases from solid tumors randomly to receive 8 mg dexamethasone before radiation therapy followed by 3 daily doses (group A), 8 mg dexamethasone followed by 3 doses of placebo (group B), or 4 doses of placebo (group C). Patients reported worst pain scores, study medication side effects, and opioid intake before treatment and thereafter daily for 14 days and on day 28. PF was defined as at least a 2-point increase on a 0 to 10 pain scale with no decrease in opioid intake or a 25% or greater increase in opioid intake with no decrease in pain score, followed by a return to baseline or lower. The primary analysis was by intention to treat with patients who had missing data classified as having a PF. RESULTS: From January 2012 to April 2016, 295 patients were randomized. PF incidence was 38% for group A, 27% for group B, and 39% for group C (P = .07). Although patients in group B had the lowest PF incidence, a relatively high percentage did not return to baseline pain levels, indicating pain progression. The mean duration of PF was 2.1 days for group A, 4.5 days for group B, and 3.3 days for group C (P = .0567). Dexamethasone postponed PF occurrence; in group A 52% occurred on days 2 to 5 versus 73% in group B and 99% in group C (P = .02). Patients in group A reported lower mean pain scores on days 2 to 5 than those in group B or C (P < .001). Side effects were similar. CONCLUSIONS: There was insufficient evidence that dexamethasone reduced the incidence of radiation-induced PF. However, dexamethasone postponed the occurrence of PF and led to lower mean pain scores on days 2 to 5.

Patterns of practice in palliative radiotherapy for bleeding tumours in the Netherlands; a survey study among radiation oncologists.

BACKGROUND AND PURPOSE: Palliative radiotherapy (RT) is one of the treatment options for bleeding tumours; a frequent symptom in patients with advanced cancer. The optimal RT schedule is however unclear. This study explores the current pattern of practice of palliative RT for bleeding tumours in the Netherlands. MATERIALS AND METHODS: An internet-based questionnaire, including respondent characteristics, factors influencing the choice of RT schedules and five patient case scenarios, was sent to all members of the Dutch Society for Radiation Oncology. Descriptive statistics were used to evaluate the results. RESULTS: The response rate was 125/374 (34%); representing 20 out of 21 Dutch RT departments. Most reported influencing factors were performance status, prognosis, patients' comfort and patients' choice. Most preferred RT schedules were 1 × 8 Gy for hematemesis, 1 × 8 Gy and 5 × 4 Gy for haemoptysis, 5 × 4 Gy for haematuria, 5 × 5 Gy for rectal bleeding, 1 × 8 Gy, 5 × 4 Gy and 10-13 × 3 Gy for vaginal bleeding. CONCLUSIONS: The current patterns of practice in the Netherlands for bleeding tumours varied considerably. Most often a single fraction is chosen (35% of all cases), followed by a five-fraction schedule (30% of all cases). The choice of an RT schedule is mainly influenced by patient related factors.

Contact of a tumour with the pleura is not associated with regional recurrence following stereotactic ablative radiotherapy for early stage non-small cell lung cancer.

BACKGROUND AND PURPOSE: The aim was to investigate the incidence of isolated regional failure following stereotactic ablative radiotherapy (SABR) and risk factors for recurrence. MATERIALS AND METHODS: Early stage non-small cell lung cancer (NSCLC) patients treated with SABR were included in this retrospective cohort study, with isolated regional recurrence (IRR) as primary endpoint, distant recurrence (DR) and overall survival (OS) as secondary endpoints. Survival analyses were performed using the cumulative incidence function (IRR and DR) or the Kaplan-Meier method (OS) and Cox proportional hazards modelling for univariate and multivariate analyses. The prognostic effect of contact between the tumour and the pleura was investigated using the CT scans used for SABR planning. RESULTS: A total of 554 patients were included, of whom 494 could be analysed for IRR. The median follow-up for surviving patients was 48.1 months. Twenty-one patients developed an IRR (4%). The cumulative incidence of IRR and DR after 1-, 2-, and 5 years was 2%, 3%, 7% and 8%, 15% and 21%, respectively. Two year OS was 71%. The presence and type of pleural contact was not associated with any of the studied outcomes. CONCLUSION: The presence, type and length of pleural contact as surrogate for visceral pleural invasion were not predictive for outcome. Further studies focussing on risk factors for occult nodal involvement, (I)RR, distant metastases and mortality in early stage NSCLC are warranted for the development of risk adapted diagnostic, treatment and follow-up strategies as more younger, operable and fitter patients receive SABR.

Individualized accelerated isotoxic concurrent chemo-radiotherapy for stage III non-small cell lung cancer: 5-Year results of a prospective study.

BACKGROUND: Stage III non-small cell lung cancer (NSCLC) still has a poor prognosis. Prior studies with individualized, accelerated, isotoxic dose escalation (INDAR) with 3D-CRT showed promising results, especially in patients not treated with concurrent chemo-radiotherapy. We investigated if INDAR delivered with IMRT would improve the overall survival (OS) of stage III NSCLC patients treated with concurrent chemotherapy and radiotherapy. PATIENTS AND METHODS: Patients eligible for concurrent chemo-radiotherapy were entered in this prospective study. Radiotherapy was given to a dose of 45 Gy/30 fractions BID (1.5 Gy/fraction), followed by QD fractions of 2 Gy until a total dose determined by the normal tissue constraints. The primary endpoint was OS, secondary endpoints were loco-regional relapses and toxicity. RESULTS: From May 4, 2009 until April 26, 2012, 185 patients were included. The mean tumor dose was 66.0 ±â€¯12.8 Gy (36-73 Gy), delivered in a mean of 39.7 fractions in an overall treatment time of 38.2 days. The mean lung dose (MLD) was 17.3 Gy. The median OS was 19.8 months (95% CI 17.3-22.3) with a 5-year OS of 24.3%. Loco-regional failures as first site of recurrence occurred in 59/185 patients (31.8%). Isolated nodal failures (INF) were observed in 3/185 patients (1.6%). Dyspnea grade 3 was seen in 3.2% of patients and transient dysphagia grade 3 in 22%. CONCLUSIONS: INDAR with IMRT concurrently with chemotherapy did not lead to a sign of an improved OS in unselected stage III NSCLC patients.

Time trends in nodal volumes and motion during radiotherapy for patients with stage III non-small-cell lung cancer.

PURPOSE: Knowledge of changes in gross tumor volume (GTV) and of GTV motion during a course of radiotherapy is necessary for accurate treatment delivery. This study describes the time trends in nodal computed tomography (CT) volume and motion for patients with locally advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: In a prospective clinical trial, 12 patients with a total of 22 positive nodes underwent a CT-positron emission tomography scan before treatment, as well as in the first and second week following start of radiotherapy. Volume changes could be measured for all nodes. For 21 nodes, the motion was measured on the basis of a respiration correlated CT (RCCT) scan. Repeated RCCT scans were available for 11 nodes to evaluate the change in motion. RESULTS: In 6 of 22 (27%) patients, the nodal volume increased >30%, whereas in 3 of 22 (14%) the volume decreased >30%. On average, the nodal volume did not change significantly (from 4.9 to 5.1 to 4.6 cm(3)). The average motion of the nodal areas was initially 5.6 +/- 2.8 mm. This motion decreased slightly during therapy but not statistically significant. However, large interpatient and internodal motion differences were observed. CONCLUSION: A large variability of changes in nodal volume between patients was observed. However, this had limited clinical impact because volumes and hence volume changes were small. The nodal motion did not change significantly during therapy. However, because of the large interpatient variability of nodal motion before treatment, internal margins for nodal areas should be calculated before radiotherapy using RCCT, such that the margins can be applied for individual patients. Repeated imaging of the nodes seems however to be of limited use because the observed individual changes in nodal volume and motion tend to fall within the commonly applied margins.

Individualized radical radiotherapy of non-small-cell lung cancer based on normal tissue dose constraints: a feasibility study.

PURPOSE: Local recurrence is a major problem after (chemo-)radiation for non-small-cell lung cancer. We hypothesized that for each individual patient, the highest therapeutic ratio could be achieved by increasing total tumor dose (TTD) to the limits of normal tissues, delivered within 5 weeks. We report first results of a prospective feasibility trial. METHODS AND MATERIALS: Twenty-eight patients with medically inoperable or locally advanced non-small-cell lung cancer, World Health Organization performance score of 0-1, and reasonable lung function (forced expiratory volume in 1 second > 50%) were analyzed. All patients underwent irradiation using an individualized prescribed 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. No concurrent chemoradiation was administered. Toxicity was scored using the Common Terminology Criteria for Adverse Events criteria. An (18)F-fluoro-2-deoxy-glucose-positron emission tomography-computed tomography scan was performed to evaluate (metabolic) response 3 months after treatment. RESULTS: Mean delivered dose was 63.0 +/- 9.8 Gy. The TTD was most often limited by the mean lung dose (32.1%) or spinal cord (28.6%). Acute toxicity generally was mild; only 1 patient experienced Grade 3 cough and 1 patient experienced Grade 3 dysphagia. One patient (3.6%) died of pneumonitis. For late toxicity, 2 patients (7.7%) had Grade 3 cough or dyspnea; none had severe dysphagia. Complete metabolic response was obtained in 44% (11 of 26 patients). With a median follow-up of 13 months, median overall survival was 19.6 months, with a 1-year survival rate of 57.1%. CONCLUSIONS: Individualized maximal tolerable dose irradiation based on normal tissue dose constraints is feasible, and initial results are promising.

Radiation dose prescription for non-small-cell lung cancer according to normal tissue dose constraints: an in silico clinical trial.

PURPOSE: Local tumor recurrence remains a major problem in patients with inoperable non-small-cell lung cancer undergoing radiotherapy. We investigated the theoretical gain in the estimated tumor control probability (TCP) using an individualized maximal tolerable dose (MTD) prescription, for both conventional and accelerated fractionation schemes. METHODS AND MATERIALS: For 64 non-small-cell lung cancer patients, five treatment plans were compared, dependent on the normal tissue dose constraints for the lung and spinal cord. The first two used a classic fractionation (2 Gy/d, 5 d/wk) to a total dose of 60 Gy (QD(classic)) or determined by the individualized MTD (QD(MTD)). The third scheme assumed a hypofractionated schedule of 2.75-Gy fractions (QD(hypofr)). The fourth and fifth assumed hyperfractionation and acceleration (1.8 Gy twice daily, either BID(classic) or BID(MTD)). The TCPs for the groups of patients were estimated. RESULTS: The mean biologic equivalent dose in 2-Gy fractions for tumor, corrected for accelerated repopulation was significantly greater for the BID(MTD) scheme (62.1 Gy) than for any other scheme (QD(classic), 47.5 Gy; QD(MTD), 52.0 Gy; QD(hypofr), 56.9 Gy; and BID(classic), 56.9 Gy; p < 0.001). Although both dose-escalation (QD(MTD)) and hypofractionation (QD(hypofr)) resulted in an increase in the mean estimated TCP of 5.6% (p < 0.001) and 14.6% (p < 0.001), respectively, compared with QD(classic), the combination of escalation and acceleration (BID(MTD)) improved the mean estimated TCP by 26.4% (p < 0.001). CONCLUSION: The results of this planning study showed a large gain in the estimated TCP using an MTD scheme with 1.8-Gy fractions BID compared with other fractionation schedules. Clinical studies implementing this concept are ongoing.

Stability of 18F-deoxyglucose uptake locations within tumor during radiotherapy for NSCLC: a prospective study.

PURPOSE: Because individual tumors are heterogeneous, including for (18)F-deoxyglucose (FDG) uptake and, most likely, for radioresistance, selective boosting of high FDG uptake zones within the tumor has been suggested. To do this, it is critical to know whether the location of these high FDG uptake patterns within the tumor remain stable during radiotherapy (RT). METHODS AND MATERIALS: Twenty-three patients with Stage I-III non-small-cell lung cancer underwent repeated FDG positron emission tomography computed tomography scans before radical RT (Day 0) and at Days 7 and 14 of RT. On all scans, the high and low FDG uptake regions were autodelineated using several standardized uptake value thresholds, varying from 34% to 80% of the maximal standardized uptake value. The volumes and overlap fractions of these delineations were calculated to demonstrate the stability of the high FDG uptake regions during RT. RESULTS: The mean overlap fraction of the 34% uptake zones at Day 0 with Days 7 and 14 was 82.8% +/- 8.1% and 84.3% +/- 7.6%, respectively. The mean overlap fraction of the high uptake zones (60%) was 72.3% +/- 15.0% and 71.3% +/- 19.7% at Day 0 with Days 7 and 14, respectively. The volumes of the thresholds varied markedly (e.g., at Day 0, the volume of the 60% zone was 16.8 +/- 20.3 cm(3)). In contrast, although the location of the high FDG uptake patterns within the tumor during RT remained stable, the delineated volumes varied markedly. CONCLUSION: The location of the low and high FDG uptake areas within the tumor remained stable during RT. This knowledge may enable selective boosting of high FDG uptake areas within the tumor.

The integration of PET-CT scans from different hospitals into radiotherapy treatment planning.

PURPOSE: To integrate PET-CT scans from different hospitals into radiotherapy treatment planning. METHODS AND MATERIALS: A cylindrical phantom with spheres of different diameters was scanned on three different Siemens Biograph PET-CT scanners in three hospitals. The spheres and cylinder were filled with 18F-FDG such that different sphere-to-background (S/B) ratios were obtained. Scans were analyzed using dedicated software for automated delineation based on standardized uptake value (SUV) and using different reconstruction parameters. RESULTS: SUV thresholding curves for different S/B ratios were obtained for the different scanners. Differences in SUV auto-contouring thresholds were found to be significant for PET-CT simulators from different radiotherapy and nuclear medicine departments. A change in PET reconstruction parameters showed a significant effect on the results. CONCLUSION: Synchronization of PET-CT imaging protocols between cooperating hospitals is important for reliable determination of SUV auto-contouring thresholds. Whenever this goal has been achieved automated SUV delineation based on a S/B ratio using PET-CT images from different institutions can reliably be performed using individually determined threshold curves.

Correlation of intra-tumour heterogeneity on 18F-FDG PET with pathologic features in non-small cell lung cancer: a feasibility study.

We evaluated the feasibility to correlate intra-tumour heterogeneity as visualized on 18F-FDG PET with histology for NSCLC. For this purpose we used an ex-vivo model. The procedure was feasible in all operated patients. We have shown that this method is suitable for correlating intra-tumour heterogeneity in tracer uptake with histology.

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.

Can an FDG-PET/CT predict tumor clearance of the mesorectal fascia after preoperative chemoradiation of locally advanced rectal cancer?

BACKGROUND AND PURPOSE: More effective preoperative treatment in locally advanced rectal cancer gives rise to a more individualized, conservative surgical treatment strategy. This, however, requires accurate information on tumor response after chemoradiation (CRT). So far, MRI and CT have failed to provide such information. Therefore, the value of a combined FDG-PET/CT in predicting tumor clearance of the mesorectal fascia (MRF) was determined. PATIENTS AND METHODS: 20 rectal cancer patients with MRF tumor invasion underwent preoperative PET/CT before and on average 6.3 weeks after CRT. The SUV(max)(maximal standard uptake value) on sequential PET/CT and the shortest distance between the outlined tumor volume and the MRF measured by using autocontouring software on post-CRT PET/CT were registered. The surgical specimen was evaluated for tumor clearance of the MRF and the tumor regression grade (TRG). RESULTS: The TRG significantly corresponded with the SUV(max)changes induced by CRT (p = 0.025), and showed a trend with the post-CRT SUV(max)(TRG 1-2 vs. TRG 3-5: SUV(max)= 3.0 vs. 5.0; p = 0.06). However, the pathologically verified tumor clearance of the MRF was not correlated with any of the tested SUV parameters nor with the shortest distance between the residual tumor and the MRF. CONCLUSION: Post-CRT PET/CT is not a useful tool for evaluating anatomic tumor changes and, therefore, not accurate in predicting tumor clearance of the MRF. However, it might be a useful tool in predicting pathologic tumor response after CRT.

Progression-Free Survival and Overall Survival Beyond 5 Years of NSCLC Patients With Synchronous Oligometastases Treated in a Prospective Phase II Trial (NCT 01282450).

INTRODUCTION: Two randomized studies have shown an increased progression-free survival (PFS) by adding a radical local treatment to systemic therapy in responding patients with oligometastatic NSCLC, but long-term data are lacking. We updated the results of our previous phase II trial with a minimal follow-up exceeding 7 years. METHODS: This is a prospective single-arm phase II trial. The main inclusion criteria were pathologically proven NSCLC stage IV with less than five metastases at primary diagnosis, amendable for radical local treatment (surgery or radiotherapy). No previous response to systemic treatment was needed. RESULTS: Forty patients were enrolled, 39 of whom were evaluable (18 men, 21 women); mean age was 62.1 ± 9.2 years (range, 44 to 81 years). Twenty-nine (74%) had N2 or N3 disease; 17 (44%) brain, 7 (18%) bone, and 4 (10%) adrenal gland metastases. Thirty-five (87%) had a single metastatic lesion. Thirty-seven (95%) of the patients received chemotherapy as part of their primary treatment. Median overall survival (OS) was 13.5 months (95% confidence interval: 7.6-19.4 months); 1-, 2-, 3-, 5-, and 6- year OS was 56.4%, 23.3%,12.8%, 10.3%, 7.7%, and 5.1%, respectively. Median PFS was 12.1 months (95% confidence interval: 9.6-14.3 months); 1-, 2-, 3-, 5-, and 6- year OS was 51.3%, 13.6%, %,12.8%, 7.7%, 7.7%, and 2.5%, respectively. Only three patients (7.7%) had a local recurrence. CONCLUSIONS: In patients who were not selected according to response to systemic treatment, the PFS at 5 years was 8%. Entering patients in trials combining local therapy with novel systemic agents (e.g., immunotherapy) remains mandatory.

The maximum uptake of (18)F-deoxyglucose on positron emission tomography scan correlates with survival, hypoxia inducible factor-1alpha and GLUT-1 in non-small cell lung cancer.

The purpose of this study was to investigate the relation between the standardised uptake value (SUV) on (18)F-fluoro-2-deoxy-glucose-positron emission tomography scan and hypoxia related markers (HIF-1alpha and CAIX), a proliferation-related marker (Ki-67) and glucose transporters (GLUT-1 and GLUT-3) in non-small cell lung cancer (NSCLC). One hundred and two patients, scheduled for complete resection, received a PET scan in Leuven or Maastricht/Aachen. The maximal SUV (SUV(max)) was correlated with survival and immunohistochemical staining patterns. The actuarial survival was worse for patients showing a high SUV(max), the best discriminative value being 8.0 (Leuven, p=0.032) and 11.0 (Maastricht, p=0.007). Tumours with a high SUV(max) expressed in a higher proportion HIF-1alpha (63.1% versus 37.9%, p=0.024) and GLUT-1 (82.9% versus 62.5%, p=0.025), than tumours with a low SUV(max). No significant difference was found in the expression of CAIX, Ki-67 and GLUT-3. This study supports preclinical data that hypoxia is associated with a higher uptake of FDG.

Feasibility of pathology-correlated lung imaging for accurate target definition of lung tumors.

PURPOSE: To accurately define the gross tumor volume (GTV) and clinical target volume (GTV plus microscopic disease spread) for radiotherapy, the pretreatment imaging findings should be correlated with the histopathologic findings. In this pilot study, we investigated the feasibility of pathology-correlated imaging for lung tumors, taking into account lung deformations after surgery. METHODS AND MATERIALS: High-resolution multislice computed tomography (CT) and positron emission tomography (PET) scans were obtained for 5 patients who had non-small-cell lung cancer (NSCLC) before lobectomy. At the pathologic examination, the involved lung lobes were inflated with formalin, sectioned in parallel slices, and photographed, and microscopic sections were obtained. The GTVs were delineated for CT and autocontoured at the 42% PET level, and both were compared with the histopathologic volumes. The CT data were subsequently reformatted in the direction of the macroscopic sections, and the corresponding fiducial points in both images were compared. Hence, the lung deformations were determined to correct the distances of microscopic spread. RESULTS: In 4 of 5 patients, the GTV(CT) was, on average, 4 cm(3) ( approximately 53%) too large. In contrast, for 1 patient (with lymphangitis carcinomatosa), the GTV(CT) was 16 cm(3) ( approximately 40%) too small. The GTV(PET) was too small for the same patient. Regarding deformations, the volume of the well-inflated lung lobes on pathologic examination was still, on average, only 50% of the lobe volume on CT. Consequently, the observed average maximal distance of microscopic spread (5 mm) might, in vivo, be as large as 9 mm. CONCLUSIONS: Our results have shown that pathology-correlated lung imaging is feasible and can be used to improve target definition. Ignoring deformations of the lung might result in underestimation of the microscopic spread.