Primary Gross Tumor Volume is Prognostic and Suggests Treatment in Upper Esophageal Cancer

Abstract Background: To aid clinicians strategizing treatment for upper esophageal squamous cell carcinoma (ESCC), this retrospective study investigated associations between primary gross tumor volume (GTVp) and prognosis in patients given surgical resection, radiotherapy, or both resection and radiotherapy. Methods: The population comprised 568 patients with upper ESCC given definitive treatment, including 238, 216, and 114 who underwent surgery, radiotherapy, or combined radiotherapy and surgery. GTVp as a continuous variable was entered into the multivariate Cox model using penalized splines (P-splines) to determine the optimal cutoff value. Propensity score matching (PSM) was used to adjust imbalanced characteristics among the treatment groups. Results: P-spline regression revealed a dependence of patient outcomes on GTVp, with 30 cm3 being an optimal cut-off for differences in overall and progression-free survival (OS, PFS). GTVp ≥ 30 cm3 was a negative independent prognostic factor for OS and PFS. PSM analyses confirmed the prognostic value of GTVp. For GTVp < 30 cm3, no significant survival differences were observed among the 3 treatments. For GTVp ≥ 30 cm3, the worst 5-year OS rate was experienced by those given surgery. The 5-year PFS rate of patients given combined radiotherapy and surgery was significantly better than that of patients given radiotherapy. The surgical complications of patients given the combined treatment were comparable to those who received surgery, but radiation side effects were significantly lower. Conclusion: GTVp is prognostic for OS and PFS in upper ESCC. For patients with GTVp ≥ 30 cm3, radiotherapy plus surgery was more effective than either treatment alone.

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NIMG-62. 68(GA)DOTATATE PET-BASED RADIATION CONTOURING CREATES SMALLER AND MORE PRECISE RADIATION VOLUMES FOR MENINGIOMA PATIENTS

Neuro-Oncology ◽

10.1093/neuonc/noab196.560 ◽

2021 ◽

Vol 23 (Supplement_6) ◽

pp. vi143-vi143

Author(s):

Haley Perlow ◽

Michael Yang ◽

Michael Siedow ◽

Yevgeniya Gokun ◽

Joseph McElroy ◽

...

Keyword(s):

Treatment Planning ◽

Pet Imaging ◽

Gross Tumor Volume ◽

Tumor Volume ◽

Radiation Treatment ◽

Progression Free Survival ◽

Mri Imaging ◽

Radiation Treatment Planning ◽

Volume Delineation ◽

The Mean

Abstract PURPOSE Radiation treatment planning for meningiomas conventionally involves MRI contrast enhanced images to define residual tumor. However, the gross tumor volume may be difficult to delineate for patients with a meningioma in the skull base, sagittal sinus, or post resection. Advanced PET imaging using 68(GA)DOTATATE PET, which has been shown to be more sensitive and specific than MRI imaging, can be used for target volume delineation in these circumstances. We hypothesize that 68(GA)DOTATATE PET scan-based treatment planning will lead to smaller radiation volumes and will detect additional areas of disease compared to standard MRI alone. METHODS Our data evaluated retrospective, deidentified, and blinded gross tumor volume (GTV) contour delineation with 7 CNS specialists (3 neuroradiologists, 4 CNS radiation oncologists) for 26 patients diagnosed with a meningioma who received both a 68(GA)DOTATATE PET and an MRI for radiation treatment planning. Both the MRI and the PET were non-sequentially contoured by each physician for each patient. RESULTS The mean MRI volume for each physician ranged from 24.14-35.52 ccs. The mean PET volume for each physician ranged from 10.59-20.54 ccs. The PET volumes were significantly smaller for 6 out of the 7 physicians. In addition, 7/26 (27%) patients had new non-adjacent areas contoured on PET by at least 6 of the 7 physicians that were not contoured by these physicians on the corresponding MRI. These new areas would not have been in the traditional MRI based volumes. CONCLUSION Our study supports that 68(GA)DOTATATE PET imaging can help radiation oncologist create smaller and more precise radiation treatment volumes. Utilization of 68(GA)DOTATATE PET may find undetected areas of disease which in turn can improve local control and progression free survival. 68(GA)DOTATATE PET guided treatment planning should be studied prospectively.

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Tumor volume as a prognostic factor in patients (pts) with locoregionally advanced head and neck squamous cell carcinoma (LAHNSCC) treated with induction chemotherapy (IC).

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e17507 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e17507-e17507

Author(s):

Daniel Moore Freitas Palhares ◽

Fernando Coutinho Batista ◽

Ana Lima Veneziani ◽

Marcos Duarte Mattos ◽

Augusto Elias Mamere ◽

...

Keyword(s):

Head And Neck ◽

Tumor Volume ◽

Univariate Analysis ◽

Stage Iv ◽

Progression Free Survival ◽

Primary Site ◽

Planning System ◽

Treatment Planning System ◽

Definitive Treatment ◽

Volumetric Change

e17507 Background: Tumor volume and the ratio of volumetric change have been demonstrated to have a prognostic role in head and neck cancers during definitive treatment in LAHNSCC. The aim of this study was to evaluate the prognostic value of tumor volume assessment during IC. Methods: We retrospectively assessed the tumor volume of 58 pts with LAHNSCC included in a prospective phase II trial which evaluated the safety of a non–5-fluorouracil-based IC (paclitaxel; cisplatin) followed by chemoradiotherapy (cisplatin; 70Gy/35fx) during 2009-2012. The volume of primary tumor (PrimV), all suspicious lymph nodes (LNV) and their sum (SumV) were determined on tomography before (CT1) and after (CT2) IC using a radiotherapy treatment planning system and the ratio of volumetric change was calculated for each variable (PrimV%, LNV% and SumV%). Results: The median follow-up time, the progression free survival (PFS) and the overall survival (OS) was 78,1, 19,3 and 22,5 months, respectively. Fifty-four pts were men, mean age 55,3±8,3y. Most had oropharynx (53%) and stage IV (72%) cancer. The median volume (cm3) was PrimV1= 25,5, LNV1= 7,5, SumV1= 40,7, PrimV2= 10,9, LNV2= 3,0, SumV2= 18,8 and median ratio of change (%) was PrimV% = 55, LNV% = 51 and SumV% = 54. Volume wa s associated with resectability (PrimV1, AUC ROC curve = 0,66, p = 0,04; LNV1, AUC = 0,85, p < 0,001; SumV1, AUC = 0,86, p < 0,001). Pts with SumV% reduction > 35% had better PFS (median 84,0 vs 10,1 months, 3y 52% vs 29%; HR = 0,39, p = 0,01) and OS (median 45,5 vs 17,0 months, 48% vs 21%; HR = 0,49, p = 0,04). On univariate analysis the PFS was correlated with T (p = 0,004), N (p = 0,01), stage (p = 0,03), primary site (p = 0,01), resectability (HR = 0,32, p = 0,001), PrimV1 (p = 0,002), SumV1 (p = 0,001), PrimV2 (p = 0,02), LNV2 (p = 0,04), SumV2 (p = 0,004), PrimV% (p = 0,04), LNV% (p = 0,003) and SumV% (p = 0,04) and OS was associated with T (p = 0,04), N (p = 0,02), stage (p = 0,04), primary site (p = 0,01), resectability (HR = 0,29, p < 0,001) PrimV1 (p = 0,003), LNV1 (p = 0,002) and SumV1 (p < 0,001). Conclusions: Tumor volume and the volumetric response during IC were associated with prognosis in LAHNSCC in the present study. Clinical trial information: NCT00959387.

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Development and Validation of Prognostic Nomograms Based on Gross Tumor Volume and Cervical Nodal Volume for Nasopharyngeal Carcinoma Patients With Concurrent Chemoradiotherapy

Frontiers in Oncology ◽

10.3389/fonc.2021.682271 ◽

2021 ◽

Vol 11 ◽

Author(s):

Cui-Dai Zhang ◽

Mei Li ◽

Ying-Ji Hong ◽

Ze-Man Cai ◽

Kai-Chun Huang ◽

...

Keyword(s):

Nasopharyngeal Carcinoma ◽

Gross Tumor Volume ◽

Concurrent Chemoradiotherapy ◽

Tumor Volume ◽

Karnofsky Performance Status ◽

Cricoid Cartilage ◽

Performance Status ◽

Progression Free Survival ◽

Training Set ◽

Kaplan Meier

PurposeOur study aimed to establish and validate prognostic nomograms based on gross tumor volume (GTV) and cervical nodal volume (CNV) for nasopharyngeal carcinoma (NPC) patients treated with two cycles of concurrent chemoradiotherapy (CCRT).MethodsFrom 2012 to 2015, 620 eligible patients who received radical treatment at the Cancer Hospital of Shantou University Medical College were recruited for a nomogram study. Variables were determined in a training set of 463 patients from 2012 to 2014 by X-tile analysis, univariate and multivariate Cox proportional hazard analyses, and the least absolute shrinkage and selection operator (LASSO). Another cohort of 157 patients in 2015 was validated with bootstrap resampling. The concordance index (C-index) and calibration curves were applied to assess its predictive discriminative and accuracy ability, while decision curve analysis (DCA), X-tile analysis and Kaplan–Meier curve for clinical application.ResultsIndependent prognostic variables for overall survival (OS) were age, GTV, CNV, cranial nerve, positive cervical lymph node laterality below the caudal border of cricoid cartilage (LNBC), and were selected for the nomogram. Optimal prognostic factors including Karnofsky performance status (KPS), age, GTV, CNV, LNBC were incorporated in the nomogram for progression-free survival (PFS). In the training set, the C-index of our nomograms for OS and PFS were 0.755 (95% CI, 0.704 to 0.807) and 0.698 (95% CI, 0.652 to 0.744). The calibration curve showed good agreement between nomogram-predicted and actual survival. DCA indicated that our nomograms were of clinical benefit.ConclusionOur nomograms are capable of effective prognostic prediction for patients with NPC.

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Survival Prediction Analysis in Glioblastoma With Diffusion Kurtosis Imaging

Frontiers in Oncology ◽

10.3389/fonc.2021.690036 ◽

2021 ◽

Vol 11 ◽

Author(s):

Yuan Li ◽

Michelle M. Kim ◽

Daniel R. Wahl ◽

Theodore S. Lawrence ◽

Hemant Parmar ◽

...

Keyword(s):

Tumor Volume ◽

Cox Model ◽

Progression Free Survival ◽

Diffusion Kurtosis Imaging ◽

Free Survival ◽

Contrast Enhanced ◽

The Mean ◽

Non Gaussian ◽

Diffusion Kurtosis ◽

Diffusion Behaviors

Simple SummaryGlioblastoma (GBM) is the most common and aggressive primary brain tumor. Diffusion kurtosis imaging (DKI) has characterized non-Gaussian diffusion behaviors in brain normal tissue and gliomas, but there are very limited efforts in investigating treatment responses of kurtosis in GBM. This study aimed to investigate whether any parameter derived from the DKI is a significant predictor of overall survival (OS). We found that the large mean, 80 and 90 percentile kurtosis values in the contrast enhanced gross tumor volume (Gd-GTV) on post-Gd T1-weighted images pre-RT were significantly associated with reduced OS. In the multivariate Cox model, the mean kurtosis Gd-GTV pre-RT after considering effects of age, extent of surgery, and methylation were significant predictors of OS. In addition, the 80 and 90 percentile kurtosis values in Gd-GTV post RT were significantly associated with progression free survival (PFS). The DKI model demonstrates the potential to predict outcomes in the patients with GBM.PurposeNon-Gaussian diffusion behaviors in gliomas have been characterized by diffusion kurtosis imaging (DKI). But there are very limited efforts in investigating the kurtosis in glioblastoma (GBM) and its prognostic and predictive values. This study aimed to investigate whether any of the diffusion kurtosis parameters derived from DKI is a significant predictor of overall survival.Methods and MaterialsThirty-three patients with GBM had pre-radiation therapy (RT) and mid-RT diffusion weighted (DW) images. Kurtosis and diffusion coefficient (DC) values in the contrast enhanced gross tumor volume (Gd-GTV) on post-Gd T1 weighted images pre-RT and mid-RT were calculated. Univariate and multivariate Cox models were used to evaluate the DKI parameters and clinical factors for prediction of OS and PFS.ResultsThe large mean kurtosis values in the Gd-GTV pre-RT were significantly associated with reduced OS (p = 0.02), but the values at mid-RT were not (p > 0.8). In the multivariate Cox model, the mean kurtosis in the Gd-GTV pre-RT (p = 0.009) was still a significant predictor of OS after adjusting effects of age, O6-Methylguanine-DNA Methyl transferase (MGMT) methylation and extent of resection. In Gd-GTV post-RT, 80 and 90 percentile kurtosis values were significant predictors (p ≤ 0.05) for progression free survival (PFS).ConclusionThe DKI model demonstrates the potential to predict OS and PFS in the patients with GBM. Further development and histopathological validation of the DKI model will warrant its role in clinical management of GBM.

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Current FDA-Approved Therapies for High-Grade Malignant Gliomas

Biomedicines ◽

10.3390/biomedicines9030324 ◽

2021 ◽

Vol 9 (3) ◽

pp. 324

Author(s):

Jacob P. Fisher ◽

David C. Adamson

Keyword(s):

Controlled Trial ◽

Malignant Gliomas ◽

Progression Free Survival ◽

Standard Of Care ◽

High Grade ◽

Tumor Treatment ◽

Free Survival ◽

Randomized Controlled ◽

Significant Survival ◽

One Year

The standard of care (SOC) for high-grade gliomas (HGG) is maximally safe surgical resection, followed by concurrent radiation therapy (RT) and temozolomide (TMZ) for 6 weeks, then adjuvant TMZ for 6 months. Before this SOC was established, glioblastoma (GBM) patients typically lived for less than one year after diagnosis, and no adjuvant chemotherapy had demonstrated significant survival benefits compared with radiation alone. In 2005, the Stupp et al. randomized controlled trial (RCT) on newly diagnosed GBM patients concluded that RT plus TMZ compared to RT alone significantly improved overall survival (OS) (14.6 vs. 12.1 months) and progression-free survival (PFS) at 6 months (PFS6) (53.9% vs. 36.4%). Outside of TMZ, there are four drugs and one device FDA-approved for the treatment of HGGs: lomustine, intravenous carmustine, carmustine wafer implants, bevacizumab (BVZ), and tumor treatment fields (TTFields). These treatments are now mainly used to treat recurrent HGGs and symptoms. TTFields is the only treatment that has been shown to improve OS (20.5 vs. 15.6 months) and PFS6 (56% vs. 37%) in comparison to the current SOC. TTFields is the newest addition to this list of FDA-approved treatments, but has not been universally accepted yet as part of SOC.

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IMMU-08. MODELING UPFRONT GLIOBLASTOMA SURGICAL RESECTION AND STEROID USE REVEALS IMMUNOSUPPRESSIVE CHANGES AND SUGGESTS THAT PERIPHERAL LYMPHOCYTE COUNTS ARE ASSOCIATED WITH TUMOR VOLUME AND PROGNOSIS

Neuro-Oncology ◽

10.1093/neuonc/noaa215.439 ◽

2020 ◽

Vol 22 (Supplement_2) ◽

pp. ii106-ii106

Author(s):

Balint Otvos ◽

Tyler Alban ◽

Matthew Grabowski ◽

Defne Bayik ◽

Robert Winkelman ◽

...

Keyword(s):

Bone Marrow ◽

Overall Survival ◽

Surgical Resection ◽

Cd8 T Cells ◽

Tumor Volume ◽

Progression Free Survival ◽

Peripheral Lymphocyte ◽

Steroid Use ◽

Free Survival ◽

Steroid Administration

Abstract Glioblastoma (GBM) and its treatment produces systemic immunosuppression, which is being targeted by immunotherapies. However, it remains unclear how surgical resection and steroids specifically in GBM alter the immune system. To further explore this issue, immunocompetent C57Bl/6 mice were intracranially inoculated with syngeneic glioma cells (GL261 and CT-2A) and growth of tumors was evaluated by MRI. Host immune cell populations were analyzed during surgical resection and steroid administration. Mice with surgically resected tumors had a longer median survival compared to mice subjected to tumor biopsies, and had increased bone marrow sequestration of both CD4 and CD8 T cells with corresponding decreased blood lymphocytes. Furthermore, physiologic doses of dexamethasone administered perioperatively decreased tumor edema, but increased the number and proliferative capacity of both marrow and circulating MDSCs while generating no survival benefit. Independent of therapy or dexamethasone, intracranial tumor volume correlated linearly with decreased CD4 and CD8 T cells in peripheral blood, and increased T cell sequestration within the bone marrow. We validated these parameters in steroid-naïve newly diagnosed GBM patients and observed decreased lymphocytes correlated linearly with increased tumor volume. When initial lymphocyte counts in both steroid-naïve and steroid-administered patients were used in univariate and multivariate models predicting progression-free survival and overall survival, decreased initial lymphocyte counts were an independent predictor of decreased progression free survival and decreased overall survival, with steroid use and initial tumor size falling out of significance during stepwise selection. Taken together, tumor volume is linearly correlated with marrow sequestration of lymphoid cells, but both surgery and steroid administration further suppress active immune responses along lymphoid and myeloid lineages. Furthermore, decreasing peripheral lymphocyte counts at diagnosis of GBM indicate an immune system less able to mount responses to the tumor and portent a worse progression free and overall survival.

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SURG-13. LASER INTERSTITIAL THERMAL THERAPY FOR RECURRENT GLIOBLASTOMA: A REVIEW OF SURVIVAL OUTCOMES COMPARED TO A MATCHED SURGICAL COHORT

Neuro-Oncology ◽

10.1093/neuonc/noaa215.860 ◽

2020 ◽

Vol 22 (Supplement_2) ◽

pp. ii206-ii206

Author(s):

Hassan Fadel ◽

Sameah Haider ◽

Jacob Pawloski ◽

Hesham Zakaria ◽

Farhan Chaudhry ◽

...

Keyword(s):

Surgical Resection ◽

Subgroup Analysis ◽

Tumor Volume ◽

Progression Free Survival ◽

Recurrent Glioblastoma ◽

Thermal Therapy ◽

Survival Outcomes ◽

Repeat Surgery ◽

Laser Interstitial Thermal Therapy ◽

Recurrent Gbm

Abstract INTRODUCTION Glioblastoma (GBM) is uniformly associated with a poor prognosis and inevitable recurrence. Management of recurrent GBM remains unclear, with repeat surgery often employed with varying degrees of success. We evaluated the efficacy of Laser Interstitial Thermal Therapy (LITT) for recurrent GBM when compared to a carefully matched cohort of patients treated with repeat surgical resection. METHODS A retrospective single-institution database was used to identify patients who underwent LITT or surgical resection of recurrent GBM between 2014-2019. LITT patients were matched with surgical resection patients according to baseline demographics, comorbidities, tumor location, and eloquence. Subgroup analysis matching similar patients for tumor volume was also completed. Overall survival (OS) and progression-free survival (PFS) were the primary endpoints. RESULTS A LITT cohort of 20 patients was matched to 50 similar patients who underwent repeat surgical resection. Baseline characteristics were similar between both cohorts apart from tumor volume, which was larger in the surgical cohort (17.5 cc vs. 4.7 cc, p< 0.01). On long-term follow-up, there was no difference in OS (HR, 0.72; 95%CI, 0.36-1.45) or PFS (HR, 0.67; 95%CI, 0.29-1.53) between the LITT and surgical cohorts when controlling for tumor volume. Subgroup analysis of 23 LITT patients matched according to tumor volume with 23 surgical patients with similar clinical characteristics also found no difference in OS (HR, 0.66; 95%CI, 0.33-1.30) or PFS (HR, 0.58; 95%CI, 0.90-1.05) between the cohorts. LITT patients had shorter length of stays (1 vs. 4 days, p< 0.001) and a higher rate of home discharge (84% vs. 67%, p=0.172) compared to the surgical cohort. CONCLUSION After matching for demographic, clinical, and tumor characteristics, there was no difference in outcomes between patients undergoing LITT compared to surgical resection for recurrent GBM. LITT patients had similar survival outcomes yet shorter hospital stays and more favorable dispositions, potentially mitigating post-treatment complications.

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Outcome of early stage Merkel carcinoma treated by exclusive radiation: a study of 53 patients

Radiation Oncology ◽

10.1186/s13014-021-01815-4 ◽

2021 ◽

Vol 16 (1) ◽

Author(s):

Manon Dubois ◽

Henry Abi Rached ◽

Alexandre Escande ◽

Frédéric Dezoteux ◽

Franck Darloy ◽

...

Keyword(s):

Cell Carcinoma ◽

Merkel Cell Carcinoma ◽

Early Stage ◽

Cox Model ◽

Combined Treatment ◽

Disease Free Survival ◽

External Beam Radiation ◽

Merkel Cell ◽

Beam Radiation ◽

Metastatic Relapse

Abstract Purpose Early stage Merkel cell carcinoma (MCC) is a rare and aggressive primary skin cancer. The standard of care for MCC is broad excision and adjuvant external beam radiation therapy (EBRT). However, for some patients, anesthesia is contraindicated, while others run the risk of serious aesthetic sequelae. In such cases, exclusive radiotherapy is an interesting alternative to surgery. Though limited data is available, this study evaluates exclusive radiotherapy for MCC, using data from the largest retrospective study to date. Methods All patients who were followed in our center between 1989 and 2019 for histologically proven early stage MCC were included in the study. They were treated either by surgery with a 2-cm clear margin followed by adjuvant radiotherapy (RT) or by exclusive RT. Survival rates with adjuvant and exclusive EBRT were analyzed using Cox model and Fine and Gray model depending on the type of survival. p value < 0.05 was considered significant. Results Eighty-four patients treated for MCC were included. Fifty-three of them (63.1%) were treated by exclusive RT, and 31 (36.9%) had surgical excision followed by adjuvant RT. Local relapse rate was 13.7% (95% CI 8.0–43.7) in the RT monotherapy group (group A) and 25.8% (95% CI 10.3–56.2) in the surgery + RT group (group B) (p = 0.42). No statistical difference was found for nodal relapse (p = 0.81), metastatic relapse (p = 0.10), disease free survival (p = 0.83) or overall survival (p = 0.98). Conclusion Our study suggests that exclusive radiotherapy for early Merkel cell carcinoma leads to a similar oncological outcome as combined treatment, with fewer aesthetic sequelae. The approach is interesting for elderly patients with comorbidities or patients for whom surgery would cause significant functional or aesthetic sequelae.

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Interobserver variability in target volume delineation in definitive radiotherapy for thoracic esophageal cancer: a multi-center study from China

Radiation Oncology ◽

10.1186/s13014-020-01691-4 ◽

2021 ◽

Vol 16 (1) ◽

Author(s):

Xiao Chang ◽

Wei Deng ◽

Xin Wang ◽

Zongmei Zhou ◽

Jun Yang ◽

...

Keyword(s):

Esophageal Cancer ◽

Gross Tumor Volume ◽

Tumor Volume ◽

Interobserver Variability ◽

Target Volume ◽

Thoracic Esophageal Cancer ◽

Target Volume Delineation ◽

Cancer Centers ◽

Definitive Radiotherapy ◽

Volume Delineation

Abstract Purpose To investigate the interobserver variability (IOV) in target volume delineation of definitive radiotherapy for thoracic esophageal cancer (TEC) among cancer centers in China, and ultimately improve contouring consistency as much as possible to lay the foundation for multi-center prospective studies. Methods Sixteen cancer centers throughout China participated in this study. In Phase 1, three suitable cases with upper, middle, and lower TEC were chosen, and participants were asked to contour a group of gross tumor volume (GTV-T), nodal gross tumor volume (GTV-N) and clinical target volume (CTV) for each case based on their routine experience. In Phase 2, the same clinicians were instructed to follow a contouring protocol to re-contour another group of target volume. The variation of the target volume was analyzed and quantified using dice similarity coefficient (DSC). Results Sixteen clinicians provided routine volumes, whereas ten provided both routine and protocol volumes for each case. The IOV of routine GTV-N was the most striking in all cases, with the smallest DSC of 0.37 (95% CI 0.32–0.42), followed by CTV, whereas GTV-T showed high consistency. After following the protocol, the smallest DSC of GTV-N was improved to 0.64 (95% CI 0.45–0.83, P = 0.005) but the DSC of GTV-T and CTV remained constant in most cases. Conclusion Variability in target volume delineation was observed, but it could be significantly reduced and controlled using mandatory interventions.

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