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

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.

Proton Radiotherapy to Reduce Late Complications in Childhood Head and Neck Cancers

In most childhood head and neck cancers, radiotherapy is an essential component of treatment; however, it can be associated with problematic long-term complications. Proton beam therapy is accepted as a preferred radiation modality in pediatric cancers to minimize the late radiation side effects. Given that childhood cancers are a rare and heterogeneous disease, the support for proton therapy comes from risk modeling and a limited number of cohort series. Here, we discuss the role of proton radiotherapy in pediatric head and neck cancers with a focus on reducing radiation toxicities. First, we compare the efficacy and expected toxicities in proton and photon radiotherapy for childhood cancers. Second, we review the benefit of proton radiotherapy in reducing acute and late radiation toxicities, including risks for secondary cancers, craniofacial development, vision, and cognition. Finally, we review the cost effectiveness for proton radiotherapy in pediatric head and neck cancers. This review highlights the benefits of particle radiotherapy for pediatric head and neck cancers to improve the quality of life in cancer survivors, to reduce radiation morbidities, and to maximize efficient health care use.

A treatment planning study comparison between supine and prone position for different lung tumour locations using CyberKnife TPS

Aim: CyberKnife is the most advanced form of stereotactic body radiotherapy (SBRT) system that uses a robotic arm to deliver highly focused beams of radiation; however, a limitation is that it only irradiates from ceiling to floor direction. In patients with posterior lungs tumour who are positioned supine, normal lung tissue may suffer undesirable radiation injuries. This study compares the treatment planning between the prone set-up and the supine set-up for lung cancer in CyberKnife SBRT to decrease normal lung dose to avoid radiation side effects. Materials and methods: A human phantom was used to generate 108 plans (54 for prone and 54 for supine) using the CyberKnife planning platform. The supine and prone plans were compared in terms of the dosimetric characteristics, delivery efficiency and plan efficiency. Results: For posterior targets, the area of low-dose exposure to normal lungs was smaller in the prone set-up than in the supine set-up. V10 of the lungs was 7·53% and 10·47% (p < 0·001) in the anterior region, and 10·78% and 8·03% (p < 0·001) in the posterior region in the supine and prone set-up plans, respectively. Conclusions: The comparison between the prone set-up and the supine set-up was investigated with regard to target coverage and dose to organs at risk. Our results may be deployed in CyberKnife treatment planning to monitor normal tissue dose by considering patient positioning. This may assist in the design of better treatment plans and prevention of symptomatic radiation pneumonitis in lung cancer patients.

Patterns of pathologic lymph nodes in anal cancer: a PET-CT-based analysis with implications for radiotherapy treatment volumes

Background This study investigates the patterns of PET-positive lymph nodes (LNs) in anal cancer. The aim was to provide information that could inform future anal cancer radiotherapy contouring guidelines. Methods The baseline [18F]-FDG PET-CTs of 190 consecutive anal cancer patients were retrospectively assessed. LNs with a Deauville score (DS) of ≥3 were defined as PET-positive. Each PET-positive LN was allocated to a LN region and a LN sub-region; they were then mapped on a standard anatomy reference CT. The association between primary tumor localization and PET-positive LNs in different regions were analyzed. Results PET-positive LNs (n = 412) were identified in 103 of 190 patients (54%). Compared to anal canal tumors with extension into the rectum, anal canal tumors with perianal extension more often had inguinal (P < 0.001) and less often perirectal (P < 0.001) and internal iliac (P < 0.001) PET-positive LNs. Forty-two patients had PET-positive LNs confined to a solitary region, corresponding to first echelon nodes. The most common solitary LN region was inguinal (25 of 42; 60%) followed by perirectal (26%), internal iliac (10%), and external iliac (2%). No PET-positive LNs were identified in the ischiorectal fossa or in the inguinal area located posterolateral to deep vessels. Skip metastases above the bottom of the sacroiliac joint were quite rare. Most external iliac PET-positive LNs were located posterior to the external iliac vein; only one was located in the lateral external iliac sub-region. Conclusions The results support some specific modifications to the elective clinical target volume (CTV) in anal cancer. These changes would lead to reduced volumes of normal tissue being irradiated, which could contribute to a reduction in radiation side-effects.

Feature Analysis of Prognostic Factors for the Radiation Toxicity Prediction of Lung Cancer Using Explainable Outcome Representation Method

BackgroundThe method of solely using a black box model for radiation toxicity prediction in patients with lung cancer has limitations in explaining the causality of the prediction results. Therefore, the feature importance of predictors was analyzed using explainable artificial intelligence.Materials and MethodsPredictions were made for the clinical prognosis through SHAP analysis (Shapley additive explanations) by using pneumonia, interstitial lung disease, chronic obstructive pulmonary disease, concurrent chemoradiation therapy, age, and dosimetric factors [lung volume receiving ≥20 Gy (V20), mean lung dose (MLD)] as prognostic factors in 110 lung cancer patients who received radiation therapy. The model was analyzed using a random forest regressor and a tree explainer; and the SHAP analysis was used to examine the features of prognostic factors affecting radiation side effects and to derive mutual impact.ResultsFor patients with grade 2 toxicity, pneumonia, MLD, and V30 were analyzed as very important factors in the prediction results. However, for grade 0 toxicity patients, V30 and MLD were identified as the predictors that had a more important impact (SHAP value=0.7) than pneumonia. In addition, pneumonia had a decisive influence on the prognosis for future side effects of grades 1 and 2 or higher, and MLD was found to have a correlation with pneumonia and SHAP value=0.38. Moreover, through this prediction model, the predicted result for patients with mild radiation pneumonitis by the ground truth of a specific patient was 1.6 (close to grade2), and MLD>20 Gy, pathology, V20, and V30 were analyzed as high-risk factors in predicting radiation side effects. The accuracy, sensitivity and specificity of the model system were 0.88, 0.79, and 0.78, respectively.ConclusionThrough this study, MLD and V30 were analyzed as important predictors of side effects, and the features of each factor were analyzed for the degree of importance by the SHAP value. To predict radiation pneumonia using this method, a personalized analysis was conducted to identify the factors that influenced each patient. Through this process, comparisons were made with the existing black box method, which confirmed that increasing the explainability can reinforce an in-depth analysis of radiation side effect prediction.

A dosimetric study to improve the quality of nodal radiotherapy in breast cancer

Objectives: Field-based planning for regional nodal breast radiotherapy (RT) used to be standard practice. This study evaluated a field-based posterior axillary boost (PAB) and two forward-planned intensity-modulated radiotherapy (IMRT) techniques, aiming to replace the first. Methods: Supraclavicular and axillary nodes, humeral head, brachial plexus, thyroid, and oesophagus were retrospectively delineated on 12 computed tomography scans. Three plans, prescribed to 40.05 Gy, were produced for each patient. Breast plans consisted of field-in-field IMRT tangential fields in all three techniques. Nodal plans consisted of three forward-planned techniques: field-based PAB (anterior and posterior boost beam), simple IMRT 1 (anterior and posterior beam with limited segments), and a more advanced IMRT two technique (anterior and fully modulated posterior beam). Results: The nodal V90% was similar between IMRT 1: mean 99.5% (SD 1.0) and IMRT 2: 99.4% (SD 0.5). Both demonstrated significantly improved results (p = 0.0001 and 0.005, respectively) compared to the field-based PAB technique. IMRT two lung V12Gy and humeral head V10Gy were significantly lower (p = 0.002, 0.0001, respectively) than the field-based PAB technique. IMRT one exhibited significantly lower brachial plexus Dmax and humeral head V5, 10, and 15Gy doses (p = 0.007, 0.013, 0.007, and 0.007, respectively) compared to the field-based PAB technique. The oesophagus and thyroid dose difference between methods was insignificant. Conclusions: Both IMRT techniques achieved the dose coverage requirements and reduced normal tissue exposure, decreasing the risk of radiation side-effects. Despite the increased cost of IMRT, compared to non-IMRT techniques 1, both IMRT techniques are suitable for supraclavicular and axillary nodal RT. Advances in knowledge: Forward-planned IMRT already resulted in significant dose reduction to organs at risk and improved planning target volume coverage. This new, simplified forward-planned IMRT one technique has not been published in this context and is easy to implement in routine clinical practice.

NCOG-66. IMPLICATION OF D-DIMER IN THE DETECTION OF DEEP VENOUS THROMBOSIS (DVT) /PULMONARY EMBOLISM (PE) IN HIGH GRADE GLIOMA PATIENTS WITHOUT CLASSIC SYMPTOMS OF DVT/PE ON OR OFF AVASTIN TREATMENT

The incidence of DVT/PE in high grade glioma patients is very high with increased risk of intracranial hemorrhage (ICH) in patients with recent surgery, Avastin and chemotherapy induced thrombocytopenia. We have frequently encountered patients with PE who presented with increased fatigue and somnolence before they developed classic symptoms of PE. It is critical that a high index of suspicion be maintained and patient screened for early detection of PE. A retrospective chart review from June 2015 to May 2020 is being performed on 500 patients with high grade glioma. D-Dimer was used as a screening test for early detection of DVT/PE. Of the 175 patients analyzed 57(32.5 %) patients had DVT/PE, 12 had DVT only and 45 patients had PE with or without DVT. Fatigue which was out of proportion to the expected chemotherapy/radiation side effects was present in 38/45 patients with PE. Classic symptoms of PE were only seen in 10/45 patients. Of 57 patients with DVT/PE with positive D-Dimer 10 asymptomatic patients were on Avastin at the time of diagnosis. The median D Dimer value for 44 positive patients was 2.43 (0.57-23.95).Of the 57 positive patients 52 (91.2%) were treated with full anticoagulation- lovenox (n-35), coumadin (n-8), eliquis (n-7) and xeralto (n-2). The IVC filter was placed in 6 patients.High risk patients were fully anticoagulated for 1-3 months. Patients with resolution of PE/DVT were switched to preventive dose of anticoagulants. Two patients had h/o hypercoagulable disorder. Two patients had symptomatic ICH on lovenox and 1 had asymptomatic sub centimeter ICH on Xeralto. Conclusion- D Dimer is very helpful in the early detection of DVT/PE in high grade glioma patients. Patients with excessive Fatigue and somnolence can be screened for PE using D-Dimer.The D Dimer screening can help with early detection of DVT/PE in patients being treated with Avastin.

Experiences when irradiating grafts and flaps for skin cancer

"Resection of skin cancer with graft or flap repair may be referred for local postoperative radiotherapy (PORT) to ensure local control." PORT needs to be delivered in a certain time frame after surgery, but this may impact on graft and flap survival. The purpose of this article is to pass on some experience our multidisciplinary team has acquired in order to assist in the management of these cases. Specifically, pertinent issues in patient assessment (history and examination), indications for PORT, the differences between a graft and a flap, and technical considerations in the prescription of radiotherapy to these are covered, accompanied by illustrative cases with appropriate photographs and diagrams. The principal findings are that a conservative approach may need to be taken to ensure graft and flap survival, with PORT reserved for a role in salvage. Other interesting cases cover the lack of acute radiation side effects in flaps; the tendency of acute radiation skin toxicity to move with gravity, and transplanted skin may have a different radiation sensitivity to that of its new environment. We hope that this article will be of use for the multidisciplinary skin oncology team. Further research is needed to validate and confirm our findings.

Preoperative radiotherapy and acridine orange photodynamic therapy causing pneumocephalus in a dog

The authors present a rare case of treatment complications in a 12-year-old spayed female Shiba Inu with left nasal transitional cell carcinoma. To control the tumour, the authors performed hypofractionated radiotherapy for five fractions over 1 week, combined with surgery, acridine orange photodynamic therapy (AO-PDT) and cribriform irradiation, one month after the initial radiotherapy. Six months later, the dog presented with neurological abnormalities (circling, pacing and reduced consciousness). Pneumocephalus was diagnosed. The irradiated left side of the olfactory bulb had become necrotic; therefore, surgery was performed to close the hole of the cribriform plate. Two years later, no visible radiation side effects or clinical signs related to intranasal tumour recurrence were detected. This case suggests that hypofractionated radiotherapy followed by surgery, AO-PDT and cribriform irradiation can contribute to tumour control. However, rare side effects, such as pneumocephalus, should be considered. Therefore, patients should be monitored carefully for adverse events after this combination.