Pretreatment Tumor Size Research Articles

Tumor size measurements predicted by digital mammography, ultrasonography, and magnetic resonance imaging in primary invasive breast cancer disease

Background and objective: The size of the tumor significantly influences the prognosis and treatment approach for breast cancer patients. The aim of this study was to find the most accurate imaging method for estimating pre-treatment tumor size in women with newly diagnosed primary invasive breast cancer by comparing the predicted tumor size obtained from mammography, ultrasonography, and magnetic resonance imaging with the pathologic size obtained from the surgical specimens. Methods: This cross-sectional study included 181 primary invasive breast cancer patients from September 2021 to March 2023. The difference in tumor size was evaluated based on imaging and pathological reports. Variables such as age, breast density, and tumor characteristics like histologic type, grade, location, and side were recorded and analyzed. The American College of Radiology Breast Imaging Reporting and Data System was used for reporting. Data analysis, performed using SPSS Statistics software, included descriptive statistics, Spearman's correlation coefficient, and Lin's index. The statistical significance level was set at P <0.05. Results: The mean tumor size was 29.68, 29.07, 28.37, and 27.7mm by mammography, ultrasonography, magnetic resonance imaging, and pathology, respectively. All diagnostic procedures revealed a statistically significant correlation with pathologic tumor size with the Spearman correlation test, P = 0.000. MRI had the highest Lin’s concordance correlation coefficient (0.93). Conclusion: The study determined that all imaging modalities were accurate in estimating tumor size when compared to the gold standard of pathological specimens and that magnetic resonance imaging outperformed digital mammography and ultrasonography.

Oncological outcomes after a pathological complete response following total neoadjuvant therapy or chemoradiotherapy for high-risk locally advanced rectal cancer in the RAPIDO trial

BackgroundA pathological complete response (pCR) following chemoradiation (CRT) or short-course radiotherapy (scRT) leads to a favourable prognosis in patients with rectal cancer. Total neo-adjuvant therapy (TNT) doubles the pCR rate, but it is unknown whether oncological outcomes remain favourable and whether the same characteristics are associated with pCR as after CRT. MethodsComparison between patients with pCR in the RAPIDO trial in the experimental [EXP] (scRT, chemotherapy, surgery, as TNT) and standard-of-care treatment [STD] (CRT, surgery, postoperative chemotherapy depending on hospital policy) groups. Primary and secondary outcomes were time-to-recurrence (TTR), overall survival (OS) and association between patient, tumour, and treatment characteristics and pCR. ResultsAmong patients with a resection within six months after preoperative treatment, 120/423 (28%) [EXP] and 57/398 (14%) [STD] achieved a pCR. Following pCR, 5-year cumulative TTR and OS rates in the EXP and STD arms were 8% vs. 7% (hazard ratio 1.04, 95%CI 0.32–3.38) and 94% vs. 93% (hazard ratio 1.41, 95%CI 0.51–3.92), respectively. Besides the EXP treatment (odds ratio 2.70, 95%CI 1.83–3.97), pre-treatment carcinoembryonic antigen (CEA) <5, pre-treatment tumour size <40 mm and cT2 were associated with pCR. Distance from the anal verge was the only characteristic with a statistically significant difference in association with pCR between the EXP and STD treatment (Pinteraction=0.042). pCR rates did not increase with prolonged treatment time. ConclusionsThe doubled pCR rate of TNT compared to CRT results in similar oncological outcomes. Characteristics associated with pCR are the EXP treatment, normal CEA, and small tumour size.

High tumor infiltrating lymphocytes are significantly associated with pathological complete response in triple negative breast cancer treated with neoadjuvant KEYNOTE-522 chemoimmunotherapy.

For patients with locally advanced triple negative breast cancer (TNBC), the standard of care is to administer the KEYNOTE-522 (K522) regimen, including chemotherapy and immunotherapy (pembrolizumab) given in the neoadjuvant setting. Pathological complete response (pCR) is more likely in patients who receive the K522 regimen than in patients who receive standard chemotherapy. Studies have shown that pCR is a strong predictor of long-term disease-free survival. However, factors predicting pCR to K522 are not well understood and require further study in real-world populations. We evaluated 76 patients who were treated with the K522 regimen at our institution. Twenty-nine pre-treatment biopsy slides were available for pathology review. Nuclear grade, Nottingham histologic grade, Ki-67, lymphovascular invasion, and tumor infiltrating lymphocytes (TIL) were evaluated in these 29 cases. For the cases that did not have available slides for review from pre-treatment biopsies, these variables were retrieved from available pathology reports. In addition, clinical staging, race, and BMI at the time of biopsy were retrieved from all 76 patients' charts. Binary logistic regression models were used to correlate these variables with pCR. At the current time, 64 of 76 patients have undergone surgery at our institution following completion of K522 and 31 (48.4%) of these achieved pCR. In univariate analysis, only TIL was significantly associated with pCR (p = 0.014) and this finding was also confirmed in multivariate analysis, whereas other variables including age, race, nuclear grade, Nottingham grade, Ki-67, lymphovascular invasion, BMI, pre-treatment tumor size, and lymph node status were not associated with pCR (p > 0.1). Our real-world data demonstrates high TIL is significantly associated with pCR rate in the K522 regimen and may potentially serve as a biomarker to select optimal treatment. The pCR rate of 48.4% in our study is lower than that reported in K522, potentially due to the smaller size of our study; however, this may also indicate differences between real-world data and clinical trial results. Larger studies are warranted to further investigate the role of immune cells in TNBC response to K522 and other treatment regimens.

Radiomics analysis with three-dimensional and two-dimensional segmentation to predict survival outcomes in pancreatic cancer.

Radiomics can assess prognostic factors in several types of tumors, but considering its prognostic ability in pancreatic cancer has been lacking. To evaluate the performance of two different radiomics software in assessing survival outcomes in pancreatic cancer patients. We retrospectively reviewed pretreatment contrast-enhanced dual-energy computed tomography images from 48 patients with biopsy-confirmed pancreatic ductal adenocarcinoma who later underwent neoadjuvant chemoradiation and surgery. Tumors were segmented using TexRad software for 2-dimensional (2D) analysis and MIM software for 3D analysis, followed by radiomic feature extraction. Cox proportional hazard modeling correlated texture features with overall survival (OS) and progression-free survival (PFS). Cox regression was used to detect differences in OS related to pretreatment tumor size and residual tumor following treatment. The Wilcoxon test was used to show the relationship between tumor volume and the percent of residual tumor. Kaplan-Meier analysis was used to compare survival in patients with different tumor densities in Hounsfield units for both 2D and 3D analysis. 3D analysis showed that higher mean tumor density [hazard ratio (HR) = 0.971, P = 0.041)] and higher median tumor density (HR = 0.970, P = 0.037) correlated with better OS. 2D analysis showed that higher mean tumor density (HR = 0.963, P = 0.014) and higher mean positive pixels (HR = 0.962, P = 0.014) correlated with better OS; higher skewness (HR = 3.067, P = 0.008) and higher kurtosis (HR = 1.176, P = 0.029) correlated with worse OS. Higher entropy correlated with better PFS (HR = 0.056, P = 0.036). Models determined that patients with increased tumor size greater than 1.35 cm were likely to have a higher percentage of residual tumors of over 10%. Several radiomics features can be used as prognostic tools for pancreatic cancer. However, results vary between 2D and 3D analyses. Mean tumor density was the only variable that could reliably predict OS, irrespective of the analysis used.

Pre-treatment Tumor Size and Tumor Growth Rate as Prognostic Predictors for Patients With Recurrent/Metastatic Squamous Cell Carcinoma of the Head and Neck Treated With Nivolumab.

The prognosis of recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN) is poor, although immune checkpoint inhibitors (ICIs), such as nivolumab, have been shown to prolong survival. We investigated the factors that predict the efficacy of nivolumab when selecting an appropriate treatment strategy for patients with R/M SCCHN. Forty-four Japanese patients with R/M SCCHN treated with nivolumab between May 2017 and October 2021 were analyzed. The primary endpoint of the study was overall survival (OS). We defined pre-treatment tumor size (PTS) as the sum of the size of all measurable lesions, and tumor growth rate (TGR) as the total growth rate of the largest tumor diameter on CT scans taken to determine treatment response, divided by the interval between CT scans. Receiver operating characteristic (ROC) curves were used to identify the cutoff points of PTS and TGR for OS. Cox proportional hazards regression analysis was performed to examine the relationships between various factors, including patient characteristics, PTS, and TGR, as well as treatment outcomes. In multivariate analysis, Eastern Cooperative Oncology Group (ECOG) performance status (PS) score ≥1, progressive disease (PD) as best overall response (BOR), and TGR >0.60%/day were independent risk factors for poor OS in patients with R/M-SCCHN. Higher TGR, poor PS, and PD as BOR may be prognostic factors in patients with R/M SCCHN.

A prognostic nomogram incorporating tumor size and lymph node size for patients with nasopharyngeal carcinoma

PurposeThe goal of this study was to establish a nomogram that included pre-treatment tumor size and lymph node (LN) size to assess personalized overall survival (OS) of patients with nasopharyngeal carcinoma (NPC). Patients and methodsThe Surveillance, Epidemiology, and End Results dataset was used to extract statistics for 1083 individuals with NPC (training cohort). In the validation cohort, 266 patients were included from the Affiliated Cancer Hospital & Institute of Guangzhou Medical University. Age, tumor–node–metastasis (TNM) stage, pre-treatment tumor size, and LN size were chosen in both the training and validation sets to build a nomogram to forecast the 3-year and 5-year OS probability using the multivariate Cox regression model. Using the C-index, calibration plot, and receiver operating characteristic (ROC) curve, the predictive model's predictive value and discriminative capacity were determined. ResultsPre-treatment tumor size, LN size, age, and TNM stage were all independent prognostic factors in the multivariate analysis. After combining these characteristics, a nomogram with a C-index of 0.7367 in the training cohort and 0.795 in the validation cohort was created, suggesting strong predictive capacity. Analysis of the ROC curve revealed that the constructed nomogram was clinically applicable. ConclusionsIn patients with NPC, the developed nomogram, which includes pre-treatment tumor size, LN size, age, and TNM stage, is a reliable predictive predictor of OS.

The Clinical Significance of Maximum Tumor Diameter on MRI in Men Undergoing Radical Prostatectomy or Definitive Radiotherapy for Locoregional Prostate Cancer.

Maximum tumor diameter (MTD) on pretreatment magnetic resonance imaging (MRI) has the potential to further risk stratify for men with prostate cancer (PCa) prior to definitive local therapy. We aim to evaluate the prognostic impact of radiographic maximum tumor diameter (MTD) in men with localized prostate cancer. From a single-center retrospective cohort of men receiving definitive treatment for PCa (radical prostatectomy [RP] or radiotherapy [RT]) with available pretreatment MRI, we conducted univariable and multivariable Cox proportional-hazards models for progression using clinical variables including age, NCCN risk group, radiographic extracapsular extension (ECE), radiographic seminal vesical invasion (SVI), and MTD. RP and RT cohorts were analyzed separately. Covariates were used in a classification and regression tree (CART) analysis and progression-free survival was estimated with the Kaplan-Meier method and groups were compared using log-rank tests. The cohort included 631 patients (n=428 RP, n=203 RT). CART analysis identified 4 prognostic groups for patients treated with RP and 2 prognostic groups in those treated with RT. In the RP cohort, NCCN low/intermediate risk group patients with MTD>=15 mm had significantly worse PFS than those with MTD <= 14 mm, and NCCN high-risk patients with radiographic ECE had significantly worse PFS than those without ECE. In the RT cohort, PFS was significantly worse in the cohort with MTD >= 23 mm than those <= 22 mm. Radiographic MTD may be a useful prognostic factor for patients with locoregional prostate cancer. This is the first study to illustrate that the importance of pretreatment tumor size may vary based on treatment modality.

Tumor shrinkage patterns of nivolumab monotherapy in metastatic renal cell carcinoma

To investigate the tumor shrinkage patterns of patients with metastatic renal cell carcinoma treated with nivolumab monotherapy. Forty-four consecutive patients with metastatic renal cell carcinoma treated with nivolumab monotherapy (81 metastatic and four primary lesions) between September 2013 and December 2020 were retrospectively analyzed. The tumor shrinkage rate of individual visceral and lymph node metastatic lesions and the primary site lesions treated with nivolumab monotherapy, as well as the association between overall survival and pretreatment tumor size, were statistically assessed. Pretreatment tumor size for the total and individual target lesions, which included kidneys, lungs, pancreas, and lymph nodes, were not correlated with tumor shrinkage rate. The tumor shrinkage rate was found to have no significant association with pretreatment tumor size between any organ. In addition, there is no significant difference in tumor shrinkage rate between larger (>median value) and smaller (<median value) pretreatment tumor size in any organ. Finally, there was no significant difference in overall survival between larger and smaller pretreatment tumor size. Pretreatment tumor size was not associated with the tumor shrinkage rate and overall survival in nivolumab monotherapy.

Early Experience Using Proton Beam Therapy for Extremity Soft Tissue Sarcoma: A Multicenter Study.

PurposeProton beam therapy (PBT) may provide an advantage when planning well-selected patients with extremity soft tissue sarcoma (eSTS), specifically for large, anatomically challenging cases. We analyzed our early experience with PBT on toxicity and outcomes.Materials and MethodsA retrospective study was performed for eSTS treated between June 2016 and October 2020 with pencil beam scanning PBT at 2 institutions. Diagnostic, treatment, and toxicity characteristics were gathered from baseline to last follow-up or death. Wound complications were defined as secondary operations for wound repair (debridement, drainage, skin graft, and muscle flap) or nonoperative management requiring hospitalization. Statistical analysis was performed with R software.ResultsTwenty consecutive patients with a median age 51.5 years (range, 19–78 years) were included. Median follow-up was 13.7 months (range, 1.7–48.1 months). Tumor presentation was primary (n = 17) or recurrent after prior combined modality therapy (n = 3). Tumor location was either lower extremity (n = 16) or upper extremity (n = 4). Radiation was delivered preoperatively in most patients (n = 18). Median pretreatment tumor size was 7.9 cm (range, 1.3 –30.0 cm). The 1-year locoregional control was 100%. Four patients (20%) had developed metastatic disease by end of follow-up. Maximum toxicity for acute dermatitis was grade 2 in 8 patients (40%) and grade 3 in 3 patients (15%). After preoperative radiation and surgical resection, acute wound complications occurred in 6 patients (35%). Tumor size was larger in patients with acute wound complications compared with those without (medians 16 cm, range [12–30.0 cm] vs 6.3 cm, [1.3–14.4 cm], P = .003).ConclusionPBT for well selected eSTS cases demonstrated excellent local control and similar acute wound complication rate comparable to historic controls. Long-term follow-up and further dosimetric analyses will provide further insight into potential advantages of PBT in this patient population.

Definitive pelvic radiation therapy improves survival in stage IVB neuroendocrine cervical carcinoma: A NeCTuR study

ObjectiveTo evaluate the survival impact of adding definitive pelvic radiation therapy (RT) to chemotherapy among patients with stage IVB neuroendocrine cervical carcinoma (NECC). MethodsWe retrospectively studied patients with FIGO 2018 stage IVB NECC diagnosed during 1998–2020 who received chemotherapy with or without definitive whole pelvic RT (concurrent or sequential). Demographic, oncologic, and treatment characteristics were summarized. Progression-free (PFS) and overall survival (OS) were plotted using the Kaplan-Meier method, and hazard ratios (HRs) were calculated using Cox regression. ResultsThe study included 71 patients. Median age was 43 years (range, 24–75). Fifty-nine patients (83%) had pure neuroendocrine histology, and 57 (80%) had pretreatment tumor size >4 cm. Fifty-six patients (79%) received chemotherapy alone with (n = 15) or without (n = 41) palliative pelvic RT, and 15 (21%) received chemotherapy and definitive pelvic RT (chemo+RT). Median follow-up time was 20.1 months (range, 11.3–170.3) for the chemo+RT group and 13.5 months (range, 0.9–73.6) for the chemotherapy-alone group. Median PFS was 10.3 months (95% CI, 7.5-∞) for the chemo+RT group vs 6.6 months (95% CI, 6.1–8.7) for the chemotherapy-alone group (p = 0.0097). At 24 months, the PFS rate was 24% for chemo+RT vs 7.8% for chemotherapy alone. Median OS was 20.3 months (95% CI, 18.5-∞) for the chemo+RT group vs 13.6 months (95% CI, 11.3–19.2) for the chemotherapy-alone group (p = 0.0013). At 24 months, the OS rate was 49.2% for chemo+RT vs 21.5% for chemotherapy alone. In a Cox regression model, definitive RT was associated with improved PFS (HR, 0.44; 95% CI, 0.23–0.83; p = 0.0119) and OS (HR, 0.31; 95% CI, 0.14–0.65; p = 0.0022). ConclusionsAddition of definitive pelvic RT to chemotherapy may improve survival in patients with stage IVB NECC.

Pretreatment risk factors for endoscopic noncurative resection of gastric cancers with undifferentiated-type components.

Endoscopic submucosal dissection (ESD) is recommended for the treatment of early gastric cancers with an undifferentiated-type component, clinically diagnosed as intramucosal lesions≤2cm, without ulceration. In the JCOG1009/1010 trial, ESD could be performed with stomach preservation in 70% of such patients whose pathological findings met the curative resection criteria. However, additional gastrectomy was required for the remaining 30%. We identified the pretreatment risk factors for noncurative resection. Post-hoc analysis indicated that 336 patients were identified in the JCOG1009/1010 trial; among them, 243 and 93 patients were categorized into the curative or noncurative resection groups, respectively, based on the pathological findings of the resected specimens. We explored the pretreatment risk factors for noncurative resection and investigated their associated pathological findings. Multivariable analysis revealed that a pretreatment tumor size>1cm was an independent risk factor for noncurative resection (odds ratio, 3.538; 95% confidence interval, 2.020-6.198, P<0.0001). Patients with a pretreatment tumor size>1cm (n=172) had a histological tumor size>2cm (22.1% vs 4.3%, odds ratio, 6.313; 95% confidence interval, 2.73-14.599, P<0.0001) and submucosal invasion (17.4% vs 9.1%, odds ratio, 2.000; 95% confidence interval, 1.032-3.877, P=0.040) more frequently as noncurative resection findings compared with those with a tumor size<1cm (n=164). Because pretreatment tumor size>1cm is an independent risk factor for noncurative resection, endoscopists should be aware that noncurative resection is not uncommon in ESD and fully explain the potential necessity for additional gastrectomy to patients before the procedure.

A preliminary study of microwave ablation for solitary T1N0M0 papillary thyroid carcinoma with capsular invasion

Objective To evaluate the feasibility, efficiency, and safety of microwave ablation (MWA) for T1N0M0 papillary thyroid carcinoma (PTC) with capsular invasion (CI). Methods The data of 69 T1N0M0 PTC with CI underwent MWA from August 2015 to January 2020 were retrospectively analyzed. All PTC nodules were pathologically confirmed by fine needle aspiration (FNA). The extended ablation was performed in all cases, that is, the ablation zone completely covered the tumor and extended the tumor edge by at least 2 mm. The strategy of fluid isolation was successfully applied before and during ablation. The strategy of multiple point ablation was applied. After ablation, the changes in tumor size at different time points, local recurrence, new lesions, lymph node metastasis (LNM), and complications were evaluated and recorded. The technical feasibility, technical success rate, and safety were analyzed. Results Based on the contrast-enhanced ultrasound results, complete ablation has been achieved in all enrolled cases after ablation. The mean maximum tumor diameter and the mean volume of PTC nodules before ablation were 0.84 ± 0.39 cm (range, 0.3–2 cm) and 0.26 ± 0.35 ml (range, 0.01–1.72 ml) respectively. The mean follow-up time was 26 ± 10 months (range, 9–48 months). Nodules in 47 cases (68.1%) completely disappeared in the follow-up period. No local recurrence was detected. The incidence of new lesions and LNM was 4.3% (3/69) and 4.3% (3/69) respectively. Further ablations have been successfully employed for all of the new lesions and LMN. Light voice changes (2.9%, 2/69) were the only major complication, which was relieved within 6 months after MWA. The sizes of the ablation zone increased firstly within 6 months after MWA compared with the pretreatment tumor size (p < 0.05). Twelve months later, the sizes were smaller than those before MWA (p < 0.05 for all). Conclusions MWA is an effective, safe, and feasible method in treating T1N0M0 PTC with CI.

The effect of fractionated gamma knife radiosurgery on visual acuity in patients with optic nerve tumor.

BackgroundStereotactic radiosurgery (SRS) method has been considered the first-line treatment option to treat patients involved with pre-optic nerve tumors. However, studies have shown that using fractionated SRS, normal tissue sparing and tumor dose can be strongly increased simultaneously. Our main goal was to illustrate the effects of fractionated SRS approach in optic nerve tumor treatment and its adjacent sensitive structures.Materials and methods19 patients involved in optic nerve tumor with clinical symptoms of vision loss were treated with Gamma Knife radiosurgery in three sessions with 12 hours intervals between them. The prescribed dose was about 6.0 ± 1.2 Gy. Patient-related parameters including pre-treatment and after-treatment tumor size, visual acuity and visual field were evaluated using the Snell chart and MRI imaging. Patients were followed for about 14 months.ResultThe overall result showed vision improvement for patients with low and moderate visual loss. However, there was no significant improvement in patients with severe visual loss. Relative improvement was observed in blind patients, although poorly. There was no evidence of growth, recurrence, or new tumor after treatment in patients.ConclusionFractionated gamma knife radiosurgery offers a safe and effective alternative for benign lesions adjacent to the optic nerve.

Metabolic Tumor Volume and Total Lesion Glycolysis Can Predict Response to Very Low Dose Radiotherapy (4 Gy) in Indolent B-Cell Lymphomas

Numerous studies have established the role of very low dose radiotherapy (VLDRT), only 4 Gy in 2 fractions, in the management of indolent non-Hodgkin's lymphoma (NHL). While objective response rates to VLDRT are excellent, there are no widely accepted biomarkers of the depth and the durability of response after VLDRT. Radiosensitivity to VLDRT is not clearly linked to clinical features, such as tumor grade, histology, prior treatments or [18F]-FDG-PET standardized uptake values (SUV). Our group has recently demonstrated that pre-treatment tumor size greater than 6 cm may predict suboptimal response to VLDRT; however, this remains an imperfect predictor, and the majority of patients selected for VLDRT have lesions smaller than 6 cm. [18F]-FDG-PET metrics like baseline metabolic tumor volume (MTV) and total lesion glycolysis (TLG) are shown to stratify patient response to chemotherapy for some NHLs, but neither has been shown to predict radiotherapy response to VLDRT. Therefore, we aimed to determine if these features could predict response to VLDRT in indolent B-cell NHLs.Between 2005 and 2018, 250 patients with follicular or marginal zone lymphoma were locally irradiated to 299 sites using 2 Gy x2. Response was assessed within 1.5-6 months of VLDRT (n=231), and local failure (LF) was assessed over a median follow-up of 29 months. Out of the 299 treated sites, 254 (85%) had a corresponding [18F]-FDG-PET/CT scan performed prior to radiotherapy. PET scans were imported into MIM, a radiotherapy contouring and planning software program, and pre-radiotherapy disease was manually defined. A uniform expansion of 0.5 cm was performed to define a larger region of interest containing the contoured lesion but accounting for technical variability in defining the tumor edges. Of the 254 lesions, 207 (81%) had a maximum SUV (SUVmax) greater than 2.5 and were considered for further analysis. PET parameters were obtained using an SUV of 2.5 as a cutoff for MTV (MTV2.5) and TLG (TLG2.5), which capture lesion bulk, and using 41% of the SUVmax as a cutoff for MTV (MTV41%) and TLG (TLG41%), which capture the most metabolically active parts of a lesion. Maximum lesion size was analyzed using 4 cm and 6 cm as predetermined cutoffs. Lesion response was analyzed using multivariate logistic LASSO regression to account for predictor multicollinearity, and receiver operating characteristic curve analysis to obtain estimates of the area under the curve (AUC). To analyze time to LF, we performed Cox proportional hazards multivariate regression using stepwise selection. PET parameters were divided in quartiles to aid in interpretability. Estimates are shown with 95% confidence intervals.A complete response (CR) was seen in 156 (68%) lesions and LF was seen in 81 (27%) lesions after VLDRT. Using size alone had similar predictive value for response (AUC: 0.57(0.49-0.65) compared to MTV2.5 (AUC:0.66 (0.57-0.74)), MTV41% (AUC:0.64 (0.56-0.73)), TLG2.5 (AUC:0.64 (0.54-0.74)), and TLG41% (AUC:0.64 (0.54,0.75)). Through LASSO logistic regression, we determined that only MTV41% > 75 th percentile was associated with lower odds of CR (odds ratio (OR):0.21 (0.08-0.53)) versus size ≥4 (OR: 0.94 (0.32, 2.73) ) with no interaction noted. Likewise, in a multivariate model of LF, TLG2.5> 75 th percentile was shown to be a better predictor of worse LF (HR: 2.44 (1.32, 4.52)) than size when considering lesions < 6 cm.In stratifying response and local control for patients receiving VLDRT for indolent lymphomas, MTV and TLG may aid in patient selection, especially for lesions smaller than 6 cm. As PET-based radiotherapy planning is routinely performed in the treatment of indolent lymphomas, these parameters are easily attained after contouring and may have immediate clinical utility. These findings may also be applicable to radiotherapy response with higher doses, and the incorporation of [18F]-FDG-PET metrics into treatment decisions is an area of active research. It remains to be seen in ongoing work whether higher-order PET radiomic features (which for instance capture heterogeneity of tumor glucose metabolism) can further improve the accuracy of [18F]-FDG-PET-based radiotherapy outcome prediction. DisclosuresMayerhoefer: Siemens: Other: Speaker Honoraria; General Electric: Other: Speaker Honoraria; Bristol Myers Squibb: Other: Speaker Honoraria.

Prediction of Response to Very Low Dose Radiotherapy (4 Gy) in Mature B-Cell Lymphomas Using Metabolic Tumor Volume

Numerous studies established the role of palliative very low dose radiotherapy (VLDRT) of only 4 Gy in 2 fractions for indolent non-Hodgkin's lymphoma (NHL). While objective response rates to VLDRT are excellent, we have no clear biomarkers of depth and durability of response. Radiosensitivity to VLDRT is not clearly linked to clinical features, such as tumor grade, histology, and PET SUV. Our group has recently demonstrated that pre-treatment tumor size may predict response to VLDRT; however, this remains an imperfect predictor. Radiomic features like baseline metabolic tumor volume (MTV) and total lesion glycolysis (TLG) stratify patient response to chemotherapy for some NHLs. Therefore, we aimed to determine if these features could predict response to VLDRT in indolent NHL.Between 2005 and 2018, 250 patients with follicular or marginal zone lymphoma were locally irradiated to 299 sites using 2 Gy x2. Response was assessed within 1.5-6 months of VLDRT (n = 231), and local failure (LF) was assessed over a median follow-up of 29 months. Out of the 299 sites, 254 had a PET/CT scan performed prior to radiotherapy. Scans were imported into MIM, and pre-radiotherapy disease was contoured with liver for normalization. PET parameters including MTV and TLG were extracted. Lesion size was analyzed using 4 cm and 6 cm as predetermined cutoffs. Lesion response was analyzed using multivariate logistic LASSO regression to account for predictor multicollinearity and area under the curve (AUC) analysis. To analyze time to LF, we performed Cox proportional hazards multivariate regression using ridge regression. PET parameters were divided in quartiles, and for significant predictors, optimal cutoffs were determined using maximally selected rank statistics. Estimates are shown with 95% confidence intervals.A complete response (CR) was seen in 156 (68%) lesions and LF was seen in 81 (27%) lesions after VLDRT. Using size alone had similar predictive value for response (AUC: 0.64 (0.59,0.70)) compared to MTV (AUC:0.70 (0.62,0.77)) and TLG (AUC:0.68 (0.61,0.75)). For lesions less than 6 cm, size, MTV and TLG had comparable predictive value for response (AUC: 0.58 (0.51,0.64), AUC:0.65 (0.56,0.75), and AUC:0.66 (0.57,0.75), respectively); however, through multivariate modeling we determined that TLG was not as robust as MTV, and MTV > 75th percentile was an improved predictor of no CR versus size ≥4 (OR: 0.26 (0.11,0.57) vs 0.77(0.30,2.08), respectively) with no interaction noted. Likewise, in a multivariate model of LF, MTV was shown to be a better predictor than size for lesions < 6 cm with an MTV ≥45 associated with worse LF (HR: 1.84 (1.14, 2.00)) compared to size > 4 cm (HR:1.31 (0.80, 2.15)).In stratifying response and local control for patients receiving VLDRT for indolent lymphomas, MTV may aid in patient selection. It remains to be seen whether higher order PET radiomic parameters can further improve the accuracy of PET-based radiotherapy outcome prediction.

Circulating Tumor Cell Assay Enables Prediction of Recurrence Following Stereotactic Body Radiotherapy for Early-Stage Non-Small Cell Lung Cancer: An Interpretable Machine Learning Study

Despite the effectiveness of stereotactic body radiotherapy (SBRT) in the local control of early-stage non-small cell lung cancer (ES-NSCLC), recurrence rates remain high. Such results may be improved with selection of high-risk patients for intensified treatment, e.g., early salvage radiotherapy or adjuvant systemic therapy/immunotherapy. We previously reported that a high level of circulating tumor cell (CTC) assay counts is prognostic for increased recurrence risks. In this study, based on the same patient cohort, we aimed to determine a threshold of CTC counts using the explainable boosting machine (EBM), a new interpretable machine learning model.Our dataset comprised de-identified patients (n = 92) with biopsy-proven or clinically presumed ES-NSCLC, enrolled between August 2013 and October 2018. All patients received SBRT to a median dose of 50 Gy. Peripheral blood samples for CTC assays were collected for each patient during pre-treatment, on-treatment (between the first and last fraction), and post-treatment at follow-up intervals of 1, 3, 6, 12, 18 and 24 months. EBM is a recently developed open-source machine learning model. It is an efficient implementation of the generalized additive model with pairwise interactions (GA2M), which yields high intelligibility without sacrificing accuracy. We used the explainable boosting classifier from EBM to predict recurrence risks, including any local, nodal or distant failures during the 2-year follow-up. In addition to the CTC counts, we selected the following clinicopathologic parameters known before the time of treatment as training features: gender, race, body mass index, smoker status, pack-years, age at enrollment, tumor size, stage, histology, and fractionation. The dataset was stratified by the recurrence label, and 5-fold split into 80% training set and 20% testing set.EBM was trained on each feature in a round-robin fashion via sequential gradient boosting. The model scored the pre-treatment CTC count (PreCTC) and tumor size as the most important features, with 9.7% and 9.3% of overall score. AJCC Stage and T Stage were scored lower at 3.7% each. The average area under the curve (AUC) was 0.713 ± 0.099. From the model, we extracted the 2-year recurrence risks as a function of PreCTC, with a peak found at 6.EBM correctly scored PreCTC as the most influential feature for predicting recurrence, in agreement with our previous findings; additionally, we extracted a PreCTC threshold of 6 for clinical stratification of ES-NSCLC patients. These results illustrate how EBM may be a useful innovative tool for machine-learning aided translation of clinical data sets.

Early Experience Using Proton Beam Therapy for Extremity Soft Tissue Sarcoma: A Multi-Institution Study

<h3>Purpose/Objective(s)</h3> Proton beam therapy (PBT) may provide an advantage when planning selected patients with extremity soft tissue sarcoma (STS), especially for larger and anatomically challenging cases. We analyzed our early experience with PBT on toxicity and outcomes. <h3>Materials/Methods</h3> A retrospective study was performed of 20 consecutive patients with extremity STS treated between June 2016 and September 2020, with pencil beam scanning PBT at two institutions with a median age 51.5 years (range, 19-78 years). Demographic, tumor, treatment, and toxicity characteristics were gathered from baseline to end of follow-up or death. Surgery was performed for all patients; chemotherapy and intraoperative electron radiotherapy boost were included for selected patients. Wound complications were defined as secondary operation for wound repair (debridement, drainage, skin graft, and muscle flap) or non-operative management requiring hospitalization. Dermatitis was graded according to the CTCAE scale. Analysis was performed with statistical software. <h3>Results</h3> All patients completed the prescribed course of PBT to a median dose of 5000 cGY RBE (range: 3000 – 6600 cGY RBE). Tumor presentation was primary (n = 17) or recurrent after prior combined modality therapy (n = 3). Tumor location was either lower extremity (n = 13) or upper extremity (n = 7). Median pre-treatment tumor size was 9.2 cm (range: 1.3 – 30.0 cm). Baseline staging for patients prior to PBT follows: 2 (10%) IA, 7 (35%) IB, 4 (20%) II, 3 (15%) IIIA, 3 (15%) IIIB, and 1 (5%) IV. Radiation was delivered pre-operatively in most patients (n = 18). Median follow-up was 13.7 months (range, 1.7 – 48.1 months). Nineteen patients (90%) were alive at the end of follow-up. Locoregional control was 100%. Four patients (20%) had developed metastatic disease by end of follow-up. Acute dermatitis was maximum grade 2 (n = 8, 40%) and grade 3 (n = 3, 15 %). After pre-operative radiation and surgical resection, acute wound complications occurred in 7 patients (39%). Intraoperative debridement and I&D, unplanned skin graft, muscle flap, and IV antibiotic use requiring hospitalization was required in 5 (25%), 3 (15%), 1 (5%), and 2 (10%), respectively. Tumor size was larger in patients with wound complications compared to no complications (median 15.3 cm [range 1.6-30.0 cm] vs 6.9cm [1.3-14.4 cm], <i>P</i> = 0.045). Factors such as patient age, tumor location, histology, chemotherapy, or IORT were not associated with wound complications. Rates of chronic G2+ pain, neuropathy, fibrosis, and lymphedema were 25%, 15%, 5%, and 5% respectively. <h3>Conclusion</h3> This early study of PBT for challenging extremity STS cases demonstrates good local control, similar acute toxicity profile, and wound complication rate comparable to photons. Long term follow-up and further dosimetric analyses will provide further insight into potential advantages of PBT in this patient population.

MC1732: Pilot/Phase II Trial of Hypofractionated Radiotherapy to the Whole Breast Alone Before Breast Conserving Surgery

To report the results of our phase II trial of breast cancer patients treated with hypofractionated whole breast radiation therapy (RT) prior to breast conserving surgery (BCS).Between 2019 and 2020, patients with cT0-T2, N0, M0 breast cancer were enrolled. Patients were treated with hypofractionated whole breast RT, 25 Gy in 5 fractions, 4-8 weeks prior to BCS. RT was delivered with proton beam therapy or photons and no RT boost or regional nodal irradiation was allowed. Pathologic assessment was performed using the Residual Cancer Burden (RCB). Toxicities were assessed according to Common Terminology Criteria for Adverse Events (CTCAE, Version 4). Quality of life (QOL) was assessed with Patient-Reported Outcomes version of the CTCAE (PRO-CTCAE), The Breast Cancer Treatment Outcome Scale (BCTOS), Linear Analogue Self-Assessment (LASA), and patient-reported outcomes measurement information system (PROMIS). Deterioration of cosmesis was defined as going from excellent/good to fair/poor or from fair to poor according to the Harvard Cosmesis Scale.Twenty-two patients were enrolled. Median follow-up was 7.1 months (range, 0.2-16.8). Median age at RT was 64.1 years (range, 44.3-76.7). Tumor characteristics included: IDC 68%, ILC 14%, DCIS 5%, other 14%; grade 1 55%, grade 2 36%, 5%; ER+HER2- 95%, ER+HER2+ 5%; right-sided 68%, left-sided 32%. The DCIS were all ER+. Pre-treatment tumor size include Tis 5% and T1 95%. Median time from RT to BCS was 8 weeks. Seven (32%) patients and 3 (14%) patients experienced grade 2+ or 3 toxicity, respectively. Overall QOL LASA and PROMIS did not change significantly from baseline (P = 0.21 and P = 0.72, respectively). There was no clinically significant change (≥1 point) in any of the BCTOS domains. Patient satisfaction with treatment was high with over 90% of patients saying they would do RT again. Only 1 (5%) patient experienced a clinical deterioration that corresponded to a 'Fair' outcome on the Harvard Cosmesis Scale. At pathologic evaluation, 14 (64%) patients had RCB-0 or RCB-1 including 3 (14%) patients with a pathologic complete response (RCB-0). No local or distant recurrences have been observed.Hypofractionated whole breast RT prior to BCS yielded excellent pathologic responses. There were low rates of toxicities and good cosmesis. Further investigation into this approach with RT before BCS is warranted.

Short term clinical outcomes of accelerated hypofractionated radiotherapy in inoperable non-small cell lung cancer patients.

This study aimed to evaluate short term clinical outcomes of accelerated hypofractionated radiotherapy (AHR T) regarding locoregional response (LRR), symptoms relief and acute toxicities in non-small cell lung cancer (NSCLC) patients. The radical treatment for inoperable NSCLC is intolerable for some patients. An alternative RT regime should be considered for them. Inoperable NSCLC patients who could not tolerate radical treatment were treated with AHRT (45 Gy in 15 fractions over three weeks) by using the 3-dimensional conformal (RT) technique. The LRR was assessed by chest computed tomography (CT) performed before and 6 weeks after RT. Relief of symptoms such as cough, dyspnoea and chest pain was evaluated during RT and 6 and 12 weeks after RT, compared with the status before RT. Treatment-related acute toxicities such as dysphagia and radiation dermatitis were observed during and 6 and 12 weeks after RT. Total 65 patients (seven patients of stage II and fifty-eight patients of stage III) were included. Partial response was seen in 70.8% of patients, and stable disease was seen in 29.2% while there was neither complete response nor progressive disease after RT. Statistically significant associations were found between tumour response vs. pre-treatment tumour size and tumour response vs. performance status of the patients. Satisfactory symptom relief was found after RT, but severe acute dysphagia and radiation dermatitis (more than grade 3) were not observed. Satisfactory LRR, symptom relief and acute toxicities were achieved by this regime. Long term studies are recommended to evaluate late toxicities and survival outcome further. TCTR20200110001.

Therapeutic outcome and related predictors of stereotactic body radiotherapy for small liver-confined HCC: a systematic review and meta-analysis of observational studies

Background and purposeStereotactic body radiotherapy (SBRT) is a promising ablative modality for hepatocellular carcinoma (HCC) especially for those with small-sized or early-stage tumors. This study aimed to synthesize available data to evaluate efficacy and explore related predictors of SBRT for small liver-confined HCC (≤ 3 lesions with longest diameter ≤ 6 cm).Materials and methodsA systematic search were performed of the PubMed and Cochrane Library databases. Primary endpoints were overall survival (OS) and local control (LC) of small HCC treated with SBRT, meanwhile, to evaluate clinical parameters associated with treatment outcome by two methods including subgroup comparisons and pooled HR meta-analysis. The secondary endpoint was treatment toxicity.ResultsAfter a comprehensive database review, 14 observational studies with 1238 HCC patients received SBRT were included. Pooled 1-year and 3-year OS rates were 93.0% (95% confidence interval [CI] 88.0–96.0%) and 72.0% (95% CI 62.0–79.0%), respectively. Pooled 1-year and 3-year LC rates were 96.0% (95% CI 91.0–98.0%) and 91.0% (95% CI 85.0–95.0%), respectively. Subgroup comparisons regarding Child–Pugh class (stratified by CP-A percentage 100%, 75–100%, 50–75%) showed there were statistically significant differences for both 1-year and 3-year OS rate (p < 0.01), while that regarding number of lesions, pretreatment situation, age (median/mean age of 65), macrovascular invasion, tumor size, and radiation dose (median BED10 of 100 Gy), there were no differences. In subgroup comparisons for LC rate, it showed number of lesions (1 lesion vs. 2–3 lesions) was significantly associated with 1-year LC rate (p = 0.04), though not associated with 3-year LC rate (p = 0.72). In subgroup comparisons categorized by other factors including pretreatment situation, age, CP-A percentage, macrovascular invasion, tumor size, and radiation dose, there were no significant differences for 1- or 3-year LC rate. To further explore the association between CP class and OS, the second method was applied by combining HR and 95% CIs. Results indicated CP-A was predictive of better OS (p = 0.001) with pooled HR 0.31 (95% CIs 0.11–0.88), which was consistent with subgroup comparison results. Concerning adverse effect of SBRT, pooled rates of grade ≥ 3 hepatic complications and RILD were 4.0% (95% CI 2.0–8.0%) and 14.7% (95% CI 7.4–24.7%), respectively.ConclusionThe study showed that SBRT was a potent local treatment for small liver-confined HCC conferring excellent OS and LC persisting up to 3 years, even though parts of included patients were pretreated or with macrovascular invasion. CP-A class was a significant predictor of optimal OS, while number of lesions might affect short term tumor control (1-year LC). Tumor size and radiation dose were not vital factors impacting treatment outcome for such small-sized HCC patients. Because of the low quality of observational studies and heterogeneous groups of patients treated with SBRT, further clinical trials should be prospectively investigated in large sample sizes.