Total Gross Tumor Volume Research Articles

Neoadjuvant Osimertinib Followed by Sequential Definitive Radiation Therapy and/or Surgery in Stage III Epidermal Growth Factor Receptor–Mutant Non-Small Cell Lung Cancer: An Open-Label, Single-Arm, Phase 2 Study

The treatment for unresectable, locally advanced stage III non-small cell lung cancer (NSCLC) is concurrent chemoradiation therapy (CRT) followed by consolidation durvalumab. This study aimed to evaluate the benefit of neoadjuvant osimertinib as an alternative therapy to this approach with the aim of reducing the radiation field. This investigation was a nonrandomized, open-label, single-arm, phase 2, prospective, proof-of-concept study. Eligible patients were classified as having treatment-naïve, nonoperable, stage III epidermal growth factor receptor-mutant NSCLC. Patients received 80 mg of oral osimertinib daily for 12 weeks before definitive radiation therapy (RT) and/or surgery. The response was assessed at weeks 6 and 12. For responders, sequential definitive RT and/or surgery were planned. Nonresponders were started on standard CRT. After RT ± surgery or CRT, patients were followed for 2 years without adjuvant therapy. The primary endpoint was the objective response rate (ORR), with September 20, 2022, set as the cut-off for data collection. Secondary endpoints were safety and the gross tumor volume (GTV), planned tumor volume (PTV), and the percentage of total lung volume minus GTV exceeding 20 Gy (V20%) before versus after osimertinib. Exploratory analyses included assessments of the presence of plasma circulating tumor-free DNA (ctDNA) before osimertinib treatment, at weeks 6 and 12, at the end of RT, and 6 weeks post-RT. Twenty-four patients were included (19 women; median age, 73 years; range, 51-82 years). Nineteen of 24 had never smoked, 20 of 24 had adenocarcinoma, 16 of 24 had exon 19 deletions, and 8 of 24 had exon 21 mutations. Participants had stage IIIA (10), IIIB (9), or IIIC (5) disease. Three patients were excluded from the analysis (1 dropped out and 2 were still undergoing osimertinib treatment at the cut-off date). The ORR to induction osimertinib was 95.2% (17 partial response, 3 complete response, and 1 progressive disease). After induction osimertinib, 13 of 20 patients were definitively radiated, 3 of 20 underwent surgery, and 5 of 20 were excluded. Four patients were restaged as stage IV (contralateral ground-glass opacities responded to osimertinib), and 1 patient withdrew informed consent. Three patients underwent surgery, one of whom was treated with RT. Two patients achieved pT1aN0, and one achieved pathologic complete response. The median GTV, PTV, and V20% before osimertinib treatment were 47.4 ± 76.9 cm3 (13.5-234.9), 227.0 ± 258.8 cm3 (77.8-929.2), and 27.1 ± 16.4% (6.2-60.3), respectively. The values after osimertinib treatment were 27.5 ± 42.3 cm3 (2.99-137.7; -48 ± 20%; P=.02), 181.9 ±198.4 cm3 (54-718.1; -31 ± 20%; P=.01), and 21.8 ± 11.7% (9.1-44.15; -24 ± 40%; P=.04), respectively. PTV/GTV/V20% reduction was associated with tumor size and central location. The median follow-up time was 28.71 months (range, 0.4-45.1 months), and median disease-free survival was not reached (mean, 30.59; standard error, 3.94; 95% confidence interval, 22.86-38.31). ctDNA was detected in 5 patients; 4 of 5 were positive for ctDNA at baseline and became negative during osimertinib induction but were again positive after osimertinib treatment was terminated. Interestingly, 3 patients who were ctDNA negative at baseline became weakly positive after RT and then were negative at follow-up. No significant adverse events were reported during the osimertinib or radiation phases. Neoadjuvant osimertinib therapy is feasible in patients with stage III lung cancer NSCLC, followed by definitive radiation and/or surgery, with an ORR of 95.2% and an excellent safety profile. Osimertinib induction for 12 weeks before definitive radiation (chemo-free) significantly reduced the radiation field by nearly 50% with a linear association with tumor size. Further studies are needed to test this chemo-free approach for long-term outcomes before practices are changed.

Deep Learning and Harmonization of Multi-Institutional Data for Automated Gross Tumor and Nodal Segmentation for Oropharyngeal Cancer

Automated tumor segmentation for oropharyngeal cancer (OPC) has the potential to improve treatment planning, response assessment, and clinical translation of imaging-based biomarkers. Deep learning has shown promise for cancer imaging segmentation, but performance for OPC tumors has been suboptimal with studies generally limited to small single-institution settings. In this study, we curated and harmonized multiple heterogeneous, multi-institutional datasets to develop and validate computed tomography (CT)-based, deep learning models for total gross tumor volume (GTV), primary (GTVp), and nodal (GTVn) segmentations.Data was obtained from The Cancer Imaging Archive (TCIA) and included 1228 CT simulation scans from OPC patients treated with definitive radiotherapy collected from 2003-2014 from four institutions that included original gross tumor volumes (GTV) as delineated by the treating radiation oncologist. GTVs were manually reviewed and ground-truth labels were harmonized to include distinct GTVp and GTVn labels. Cases were split randomly, such that 70% of cases were used for model training, 15% for tuning, and 15% for independent performance testing. Utilizing a modified 3D UNET-based architecture, models were trained and tuned to predict total GTV, GTVp and GTVn. Model performance was assessed by measuring precision, recall, and dice score coefficient (DSC) when comparing deep learning-generated to ground truth volumes in the independent test set. Patients without contrast-enhanced CT were excluded from the GTVp model a priori, given the importance of contrast in delineating primary tumor.Algorithms' median performance on test sets with 95% confidence intervals. GTVp test set limited to contrast-enhanced scans. Within the total dataset (n = 1228), median age was 59, cases were 82% male, and HPV status was 49% positive, 16% negative, and 35% unknown. Tumor staging was 45% T3-4, 54% T1-T2, and 1% T0/X. Nodal staging was 75% N2-N3 and 25% N0-1. Overall, the GTVn model had the highest performance (median DSC: 0.76; 95% CI: 0.73, 0.77), followed by total GTV (median DSC: 0.71; 95% CI: 0.68, 0.73), and GTVp (median DSC 0.68; 95% CI: 0.63, 0.71).Deep learning with multiple harmonized data sources can yield effective models for OPC primary and nodal segmentation using CT alone. The utility of these models will depend on the clinical use case and will be explored on further investigation, though current model performance metrics, particularly for nodal segmentation, are likely adequate for prospective testing in clinical and research applications.

Predictive Values of MRI and PET Derived Quantitative Parameters for Patterns of Failure in Both p16+ and p16- High Risk Head and Neck Cancer.

Purpose: FDG-PET adds to clinical factors, such tumor stage and p16 status, in predicting local (LF), regional (RF), and distant failure (DF) in poor prognosis locally advanced head and neck cancer (HNC) treated with chemoradiation. We hypothesized that MRI-based quantitative imaging (QI) metrics could add to clinical predictors of treatment failure more significantly than FDG-PET metrics.Materials and methods: Fifty four patients with poor prognosis HNCs who were enrolled in an IRB approved prospective adaptive chemoradiotherapy trial were analyzed. MRI-derived gross tumor volume (GTV), blood volume (BV), and apparent diffusion coefficient (ADC) pre-treatment and mid-treatment (fraction 10), as well as pre-treatment FDG PET metrics, were analyzed in primary and individual nodal tumors. Cox proportional hazards models for prediction of LRF and DF free survival were used to test the additional value of QI metrics over dominant clinical predictors.Results: The mean ADC pre-RT and its change rate mid-treatment were significantly higher and lower in p16– than p16+ primary tumors, respectively. A Cox model identified that high mean ADC pre-RT had a high hazard for LF and RF in p16– but not p16+ tumors (p = 0.015). Most interesting, persisting subvolumes of low BV (TVbv) in primary and nodal tumors mid-treatment had high-risk for DF (p < 0.05). Also, total nodal GTV mid-treatment, mean/max SUV of FDG in all nodal tumors, and total nodal TLG were predictive for DF (p < 0.05). When including clinical stage (T4/N3) and total nodal GTV in the model, all nodal PET parameters had a p-value of >0.3, and only TVbv of primary tumors had a p-value of 0.06.Conclusion: MRI-defined biomarkers, especially persisting subvolumes of low BV, add predictive value to clinical variables and compare favorably with FDG-PET imaging markers. MRI could be well-integrated into the radiation therapy workflow for treatment planning, response assessment, and adaptive therapy.

Long-Term Outcomes of Phase 1 and 2 Studies of SBRT for Hepatic Colorectal Metastases

To report mature outcomes of prospective phase 1 and 2 studies of stereotactic body radiation therapy (SBRT) for the treatment of colorectal liver metastases (CLMs). Patients with histologically confirmed CLMs unsuitable for resection or standard therapies were eligible for sequential phase 1 and 2 studies conducted from 2003 to2012. Of 60 patients treated, 82% had received previous chemotherapy, 23% had undergone previous focal liver treatment, and 38% had extrahepatic disease at the time of SBRT. The median number of gross tumor volume (GTV) targets per patient was 1 (range, 1-6), with a median total target volume of 117.7cm3 (range, 6.7-3115.4cm3). The median minimum dose to the GTV was 37.6Gy (range, 22.7-62.1Gy) in 6 fractions over a period of 2weeks. Other than 1 case of grade 3 nausea, there were no acute toxicities greater than grade 2. With a median follow-up period of 28.1months for survivors, no gastrointestinal bleed or biliary or liver toxicity was seen.The local control rate per lesion at 1 and 4years was 49.8% and 26.2%, respectively. Increasing minimum dose to the GTV was associated with improved local control (P=.003).Median overall survival was 16.0months (95% confidence interval, 11.9-20.5months). On multivariate analysis, improved survival was associated with smaller total GTV (P=.017), performance status of 0 or 1 (P=.007), no extrahepatic disease at the time of treatment (P=.005), and local control of targeted liver disease (P=.001). Two long-term survivors remain disease free at 49 and 125months. Six-fraction SBRT for CLM is safe and may be associated with long-term cure. Local control was significantly associated with delivered dose and was lower than seen in other studies using a higher SBRT dose. Survival was associated with smaller tumor volume, absence of extrahepatic disease, performance status of 0 or 1, and local control of treated liver lesions.

Gross tumor volume is the prognostic factor for squamous cell esophageal cancer patients treated with definitive radiotherapy.

To investigate whether gross tumor volume (GTV) defined on radiotherapy planning scans a prognostic factor for esophageal squamous cell carcinoma (ESCC) patients treated with definitive radiotherapy. From 2008 to 2011, 187 ESCC patients who were treated with definitive radio(chemo)therapy were analyzed retrospectively. Tumor volumes such as GTV, gross tumor volume of primary esophageal cancer (GTV-P), and gross tumor volume of metastases lymph nodes (GTV-N) were computed by Philips Healthcare radiation therapy planning system (Pinnacle 8.0). Kaplan-Meier cumulative probability and Cox proportional hazards regression models were used to assess the effect of the clinical factors along with tumor volume on progression-free survival (PFS) and overall survival (OS). In the univariate analysis, fraction dose, TNM stage, total radiation dose, GTV, GTV-P, and GTV-N were all significantly associated with both OS and PFS (P<0.05). While in multivariate analysis, GTV and fraction dose were significantly associated with both OS and PFS (adjusted P<0.05) with adjustment for age, sex, smoking status, chemotherapy, fraction dose, GTV, and radiation dose. GTV may serve as a good prognostic factor for ESCC patients treated with definitive radiotherapy. Larger prospective studies are needed to validate these findings.

Decision Trees Predicting Tumor Shrinkage for Head and Neck Cancer

To develop decision trees predicting for tumor volume reduction in patients with head and neck (H&N) cancer using pretreatment clinical and pathological parameters. Forty-eight patients treated with definitive concurrent chemoradiotherapy for squamous cell carcinoma of the nasopharynx, oropharynx, oral cavity, or hypopharynx were retrospectively analyzed. These patients were rescanned at a median dose of 37.8 Gy and replanned to account for anatomical changes. The percentages of gross tumor volume (GTV) change from initial to rescan computed tomography (CT; %GTVΔ) were calculated. Two decision trees were generated to correlate %GTVΔ in primary and nodal volumes with 14 characteristics including age, gender, Karnofsky performance status (KPS), site, human papilloma virus (HPV) status, tumor grade, primary tumor growth pattern (endophytic/exophytic), tumor/nodal/group stages, chemotherapy regimen, and primary, nodal, and total GTV volumes in the initial CT scan. The C4.5 Decision Tree induction algorithm was implemented. The median %GTVΔ for primary, nodal, and total GTVs was 26.8%, 43.0%, and 31.2%, respectively. Type of chemotherapy, age, primary tumor growth pattern, site, KPS, and HPV status were the most predictive parameters for primary %GTVΔ decision tree, whereas for nodal %GTVΔ, KPS, site, age, primary tumor growth pattern, initial primary GTV, and total GTV volumes were predictive. Both decision trees had an accuracy of 88%. There can be significant changes in primary and nodal tumor volumes during the course of H&N chemoradiotherapy. Considering the proposed decision trees, radiation oncologists can select patients predicted to have high %GTVΔ, who would theoretically gain the most benefit from adaptive radiotherapy, in order to better use limited clinical resources.

Role of PET/CT in treatment planning for head and neck cancer patients undergoing definitive radiotherapy.

In this study, we aimed to investigate the benefits of 18F-deoxyglucose positron emission tomography/computed tomography (FGD-PET/CT) imaging for staging and radiotherapy planning in patients with head and neck cancer undergoing definitive radiotherapy. Thirty-seven head and neck cancer patients who had undergone definitive radiotherapy and PET/CT at the Uludag University Medical Faculty Department of Radiation Oncology were investigated in order to determine the role of PET/CT in staging and radiotherapy planning. The median age of this patient group of 32 males and 5 females was 57 years (13-84years). The stage remained the same in 18 cases, decreased in 5 cases and increased in 14 cases with PET/CT imaging. Total gross tumor volume (GTV) determined by CT (GTVCT-Total) was increased in 32 cases (86.5%) when compared to total GTV determined by PET/CT (GTVPET/CT-Total). The GTV of the primary tumor determined by PET/CT (GTVPET/CT) was larger in 3 cases and smaller in 34 cases compared to that determined by CT (GTVCT). The GTV of lymph nodes determined by PET/CT (GTVLNPET/CT) was larger in 20 cases (54%) and smaller in 12 cases (32.5%) when compared to GTV values determined by CT (GTVLNCT). No pathological lymph nodes were observed in the remaining five cases with both CT and PET/ CT. We can conclude that PET/CT can significantly affect both pretreatment staging and assessed target tumor volume in patients with head and neck cancer. We therefore recommend examining such cases with PEC/CT before treatment.

Interobserver Variability in Target Definition for Hepatocellular Carcinoma With and Without Portal Vein Thrombus: Radiation Therapy Oncology Group Consensus Guidelines

Defining hepatocellular carcinoma (HCC) gross tumor volume (GTV) requires multimodal imaging, acquired in different perfusion phases. The purposes of this study were to evaluate the variability in contouring and to establish guidelines and educational recommendations for reproducible HCC contouring for treatment planning. Anonymous, multiphasic planning computed tomography scans obtained from 3 patients with HCC were identified and distributed to a panel of 11 gastrointestinal radiation oncologists. Panelists were asked the number of HCC cases they treated in the past year. Case 1 had no vascular involvement, case 2 had extensive portal vein involvement, and case 3 had minor branched portal vein involvement. The agreement between the contoured total GTVs (primary + vascular GTV) was assessed using the generalized kappa statistic. Agreement interpretation was evaluated using Landis and Koch's interpretation of strength of agreement. The S95 contour, defined using the simultaneous truth and performance level estimation (STAPLE) algorithm consensus at the 95% confidence level, was created for each case. Of the 11 panelists, 3 had treated >25 cases in the past year, 2 had treated 10 to 25 cases, 2 had treated 5 to 10 cases, 2 had treated 1 to 5 cases, 1 had treated 0 cases, and 1 did not respond. Near perfect agreement was seen for case 1, and substantial agreement was seen for cases 2 and 3. For case 2, there was significant heterogeneity in the volume identified as tumor thrombus (range 0.58-40.45 cc). For case 3, 2 panelists did not include the branched portal vein thrombus, and 7 panelists contoured thrombus separately from the primary tumor, also showing significant heterogeneity in volume of tumor thrombus (range 4.52-34.27 cc). In a group of experts, excellent agreement was seen in contouring total GTV. Heterogeneity exists in the definition of portal vein thrombus that may impact treatment planning, especially if differential dosing is contemplated. Guidelines for HCC GTV contouring are recommended.

Dose escalation to high-risk sub-volumes based on non-invasive imaging of hypoxia and glycolytic activity in canine solid tumors: a feasibility study

IntroductionGlycolytic activity and hypoxia are associated with poor prognosis and radiation resistance. Including both the tumor uptake of 2-deoxy-2-[18 F]-fluorodeoxyglucose (FDG) and the proposed hypoxia tracer copper(II)diacetyl-bis(N4)-methylsemithio-carbazone (Cu-ATSM) in targeted therapy planning may therefore lead to improved tumor control. In this study we analyzed the overlap between sub-volumes of FDG and hypoxia assessed by the uptake of 64Cu-ATSM in canine solid tumors, and evaluated the possibilities for dose redistribution within the gross tumor volume (GTV).Materials and methodsPositron emission tomography/computed tomography (PET/CT) scans of five spontaneous canine solid tumors were included. FDG-PET/CT was obtained at day 1, 64Cu-ATSM at day 2 and 3 (3 and 24 h pi.). GTV was delineated and CT images were co-registered. Sub-volumes for 3 h and 24 h 64Cu-ATSM (Cu3 and Cu24) were defined by a threshold based method. FDG sub-volumes were delineated at 40% (FDG40) and 50% (FDG50) of SUVmax. The size of sub-volumes, intersection and biological target volume (BTV) were measured in a treatment planning software. By varying the average dose prescription to the tumor from 66 to 85 Gy, the possible dose boost (D B ) was calculated for the three scenarios that the optimal target for the boost was one, the union or the intersection of the FDG and 64Cu-ATSM sub-volumes.ResultsThe potential boost volumes represented a fairly large fraction of the total GTV: Cu3 49.8% (26.8-72.5%), Cu24 28.1% (2.4-54.3%), FDG40 45.2% (10.1-75.2%), and FDG50 32.5% (2.6-68.1%). A BTV including the union (∪) of Cu3 and FDG would involve boosting to a larger fraction of the GTV, in the case of Cu3∪FDG40 63.5% (51.8-83.8) and Cu3∪FDG50 48.1% (43.7-80.8). The union allowed only a very limited D B whereas the intersection allowed a substantial dose escalation.ConclusionsFDG and 64Cu-ATSM sub-volumes were only partly overlapping, suggesting that the tracers offer complementing information on tumor physiology. Targeting the combined PET positive volume (BTV) for dose escalation within the GTV results in a limited D B . This suggests a more refined dose redistribution based on a weighted combination of the PET tracers in order to obtain an improved tumor control.

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

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. 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 ). 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. 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.

Volumetric staging in oropharyngeal cancer patients treated with definitive IMRT

The superiority of volumetric staging (VS) over TNM/TNM-grouping system was previously prospectively tested in our head neck cancer population treated with intensity-modulated radiotherapy (IMRT); gross tumor volume (GTV) was the strongest predictor for disease control. Aim of this work was to specifically assess the prognostic value of VS in oropharyngeal cancer (OC). Between 04/2002 and 12/2011, 277 consecutive OC patients underwent definitive IMRT. Mean/median follow-up was 33/27 months (3-113). Three volumetric cut-offs were used (resulting in 4 GTV subgroups: 1-15 cc (14%), 16-70 cc (62%), 71-130 cc (20%), >130 cc (4%)). Outcome in the OC subgroup was prospectively assessed with VS and compared with that resulting from TNM and AJCC staging. Primary GTV was most reliably predicting local control (p<0.0001), all other outcome parameters were predicted best by the total GTV (p<0.0001). This is -to our knowledge- the first volumetric staging system for OC, and was found to be most reliable in predicting outcome in OC patients treated with IMRT.

Impact of tumor volume and systemic therapy on outcome in patients undergoing IMRT for large volume head neck cancer

BackgroundFormer prospective analyses revealed gross tumor volume (GTV) as the most reliable parameter to statistically significantly predict disease control in head neck cancer (HNC) patients treated with definitive intensity modulated radiation therapy (IMRT) +/-concomitant systemic therapy. The most 'unfavourable' subgroup was characterized by total GTV (tGTV) of > 70 cc, translating in ~50 and 65% 3-year disease free (DFS) and overall survival (OAS, vs 68% and 88% in tGTV < 70 cc, p = 0.001 and 0.0001), and ~25% distant spread (vs 6% for tGTV < 70 cc, p < 0.0001).The aim of this report was to analyze whether there is a subgroup out of patients with tGTV > 70 cc, which only marginally benefits from intensive curative treatment.ResultsBetween 03/2002-03/2011, 112 HNC patients with tGTV > 70 cc were definitively irradiated with curative intention. Mean tGTV was 104 cc (71-251). 98/112 (88%) patients underwent systemic therapy. Parameters with potential impact on disease outcome were retrospectively tested. The 3-year local-regional control (LRC), DFS and OAS rates were 61%, 50%, and 58%. The used cut-off value of 130 cc revealed an inverse association between tGTV and outcome. Patients able to undergo any systemic therapy (n = 98, mean tGTV0 103 cc, mean age 60 years) showed a satisfying and significantly superior outcome compared to the subgroup with radiation alone (n = 14, mean tGTV 99 cc, mean age 73 years), with 53% vs 17% 3-year DFS (p = 0.01). Radiation alone for tGTV > 130 cc failed to aim its curative goal in 3/3 patients.ConclusionPatients with tGTV > 70 cc unable to undergo any systemic therapy represented a subgroup in which disease control was achievable in < 20% following curatively intended IMRT. Prospective testing of a larger sample size is needed to evaluate, if radiation alone for tGTV >~130 cc fails to meet its curative aim.

Delineation of Gross Tumor Volume (GTV) for Radiation Treatment Planning of Locally Advanced Rectal Cancer Using Information From MRI or FDG-PET/CT: A Prospective Study

Accurate delineation of target volumes is important to maximize radiation dose to the tumor and minimize it to nontumor tissue. Computed tomography (CT) and magnetic resonance imaging (MRI) are standard imaging modalities in rectal cancer. The aim was to explore whether functional imaging with F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET), combined with CT (FDG-PET/CT) gives additional information to standard pretreatment evaluation and changes the shape and size of the gross tumor volume (GTV). From 2007 to 2009, 77 consecutive patients with locally advanced rectal cancer were prospectively screened for inclusion in the study at two university hospitals in Sweden, and 68 patients were eligible. Standard GTV was delineated using information from clinical examination, CT, and MRI (GTV-MRI). Thereafter, a GTV-PET was defined in the fused PET-CT, and the target volume delineations were compared for total volume, overlap, and mismatch. Pathologic uptake suspect of metastases was also registered. The median volume of GTV-MRI was larger than that of GTV-PET: 111 cm(3) vs. 87 cm(3) (p < 0.001). In many cases, the GTV-MRI contained the GTV defined on the PET/CT images as subvolumes, but when a GTV total was calculated after the addition of GTV-PET to GTV-MRI, the volume increased, with median 11% (range, 0.5-72%). New lesions were seen in 15% of the patients for whom PET/CT was used. FDG-PET/CT facilitates and adds important information to the standard delineation procedure of locally advanced rectal cancer, mostly resulting in a smaller GTV, but a larger total GTV using the union of GTV-MRI and GTV-PET. New lesions were sometimes seen, potentially changing the treatment strategy.

Tumor Volume as a Potential Imaging-Based Risk-Stratification Factor in Trimodality Therapy for Locally Advanced Non-small Cell Lung Cancer

The role of trimodality therapy for locally advanced non-small cell lung cancer (NSCLC) continues to be defined. We hypothesized that imaging parameters on pre- and postradiation positron emission tomography (PET)-computed tomography (CT) imaging are prognostic for outcome after preoperative chemoradiotherapy (CRT)/resection/consolidation chemotherapy and could help risk-stratify patients in clinical trials. We enrolled 13 patients on a prospective clinical trial of trimodality therapy for resectable locally advanced NSCLC. PET-CT was acquired for radiation planning and after 45 Gy. Gross tumor volume (GTV) and standardized uptake value were measured at pre- and post-CRT time points and correlated with nodal pathologic complete response, loco-regional and/or distant progression, and overall survival. In addition, we evaluated the performance of automatic deformable image registration (ADIR) software for volumetric response assessment. All patients responded with average total GTV reductions after 45 Gy of 43% (range: 27-64%). Pre- and post-CRT GTVs were highly correlated (R² = 0.9), and their respective median values divided the patients into the same two groups. ADIR measurements agreed closely with manually segmented post-CRT GTVs. Patients with GTV ≥ median (137 ml pre-CRT and 67 ml post-CRT) had 3-year progression-free survival (PFS) of 14% versus 75% for GTV less than median, a significant difference (p = 0.049). Pre- and post-CRT PET-standardized uptake value did not correlate significantly with pathologic complete response, PFS, or overall survival. Preoperative CRT with carboplatin/docetaxel/45 Gy resulted in excellent response rates. In this exploratory analysis, pre- and post-CRT GTV predicted PFS in trimodality therapy, consistent with our earlier studies in a broader cohort of NSCLC. ADIR seems robust enough for volumetric response assessment in clinical trials.

Margin on Gross Tumor Volume and Risk of Local Recurrence in Head-and-Neck Cancer

To determine whether the method or extent of construction of the high-dose clinical target volume (CTV) and high-dose planning target volume (PTV) in intensity-modulated radiation therapy (IMRT) for head-and-neck cancer are associated with an increased risk of locoregional failure. Patients with nasopharyngeal, oropharyngeal, oral cavity, hypopharyngeal, or laryngeal squamous cell carcinomas treated definitively with IMRT were included. All patients without local relapse had a minimum follow-up of 12 months. Median follow-up for all patients was 24 months. Treatment plans of 85 available patients were reviewed, and the gross tumor volume (GTV) to PTV expansion method was estimated. The GTVs were expanded volumetrically in 71 of 85 patients, by a median of 15 mm (range, 4-25 mm). An anatomic component to the expansion of GTV was used in 14 of 85 patients. Eighteen patients failed locoregionally, for an actuarial locoregional control rate of 77.2% at 2 years. There was no significant difference in locoregional control between patients with GTVs expanded volumetrically vs. those with a component of anatomic expansion. In patients with GTVs expanded volumetrically, no increase in risk of local failure was seen in patients with a total GTV expansion of < or =15 mm. In this retrospective study, there was not an increased risk of local failure using smaller margins or expanding GTVs volumetrically when treating head-and-neck cancer patients definitively with IMRT.

Prognostic impact of tumor volumetry in patients with locally advanced head-and-neck carcinoma (non-nasopharyngeal) treated by radiotherapy alone or combined radiochemotherapy in a randomized trial

Purpose Tumor volume (TV) is one of the main reported factors determining the outcome of treatment in head-and-neck carcinomas. In this study, the prognostic impact of TV was explored in the context of a randomized trial with the patients assigned to receive standard radiotherapy (RT) alone or RT plus platinum compounds (RT alone, RT plus cisplatin, or RT plus carboplatin). Methods and materials The tumor outlines were traced and digitized on each pretreatment CT slice for each of the 101 patients studied. Taking into account the magnification factor of the scan and CT slice thickness, a computer with specifically designed software calculated the TV in cubic centimeters. Results The median overall survival for the whole group of patients was 21.6 months (95% confidence interval, 13.0–30.2) and the 3-year survival rate was 40%. The addition of platinum compounds to RT (Groups 2 and 3) significantly improved the survival rate (RT alone vs. RT plus cisplatin, hazard ratio 0.36, p = 0.002; RT alone vs. RT plus carboplatin, hazard ratio 0.53, p = 0.029). In univariate analysis, the most significant parameters for survival were treatment group, total gross tumor volume (TGTV), complete response, nodal GTV, primary GTV, and performance status. In multivariate analysis, treatment group, TGTV, gender, and primary site were independent prognostic factors for survival. A prognostic threshold of 22.8 cm 3 was detected for TGTV. Patients with a TGTV of <22.8 cm 3 were more likely to achieve a complete response and had a median survival of 45.3 months, and those with a TGTV >22.8 cm 3 had a median survival of 12.3 months (log–rank test, p = 0.0102). Conclusion The prognostic significance of the TGTV was confirmed and a cutoff value of 22.8 cm 3 derived. Our data indicated that locally advanced head-and-neck carcinomas should not be treated by standard (once-daily) RT alone. Tumor size and disease subsite should be taken into account in future randomized trials to increase their statistical power.