Macroscopic Tumor Research Articles

Dose-Escalated SBRT for Borderline and Locally Advanced Pancreatic Cancer: Resectability Rate and Pathological Results of a Multicenter Prospective Study

Objective: We demonstrated for the first time the safety and feasibility of escalating up to 55 Gy/11 Gy/fr/5fr in borderline (BRPC)/unresectable locally advanced pancreatic cancer (LAPC), using the standard LINAC platform. The aim of the present study is to assess for the first time the impact of this high-dose neoadjuvant stereotactic ablative radiotherapy (SABRT) protocol on tumor resectability and pathological responses. Materials/Methods: From June 2017 to December 2022, patients with BRPC/LAPC were treated with neoadjuvant chemotherapy (ChT) and SABRT-escalated doses of SIB at 45 Gy, 50 Gy, and up to 55 Gy (BED ≥ 100). Radiological evaluation was conducted with a CT scan 6-8 weeks post-treatment to determine resectability status based on established criteria (SAR/APA2014). Surgical decisions were made by the multidisciplinary tumor board of the participating institutions. Pathological assessments post-surgery used criteria from the College of American Pathologists (CAP), categorizing resection status as R0 (negative margins), R1 (microscopic tumor margins), and R2 (macroscopic tumor margins). Tumor response was evaluated with the Tumor Response Scoring (TRS) system, as G0 (no viable cancer cells), G1 (single cells or rare small groups), G2 (residual cancer with evident regression), and G3 (extensive residual cancer). Results: Thirty-three patients (p) were included: 39.4% (13p) BRPC/60.6% (20p) LAPC. After ChT-SABRT, 45.5% (15p) were considered resectable, with 11/13 (84.6%) BRPC and 4/20 (20%) LAPC (p < 0.0001). One patient refused surgery and other patient died of COVID sepsis. Two more patients had disseminated disease at surgery. Among the 11 patients who underwent full surgery, all patients achieved either clean margins R0: 72.7% (8p) or microscopic affected margins R1: 27.3% (3p). TRS scores were G1: 27.3% (3p), G2: 54.5% (6p), and G3: 18.2% (2p). The present follow-up (FUP) was closed on 1 November 2024 (23.55 months, range: 6–71 months). The mean freedom from local progression as the first cause of disease failure was 43.30 ± 3.09 (37.23–49.38), and the median was not reached. The actuarial 1- and 2-year rates for freedom from local relapse as a first cause of disease failure were 92.3% (87.7–93.3%) and 79.7% (79.7–87.7%), respectively. Conclusions: Neoadjuvant ChT-SABRT in LAPC improves resectability rates and induces relevant tumor regression. These promising findings should be validated by larger sample sizes and extended follow-up.

Optical molecular imaging in oral- and oropharyngeal squamous cell carcinoma using a novel uPAR-targeting near-infrared imaging agent FG001 (ICG-Glu-Glu-AE105): An explorative phase II clinical trial.

Background: In oral and oropharyngeal squamous cell carcinoma (OSCC, OPSCC), frequent inadequate surgical margins highlight the importance of precise intraoperative identification and delineation of cancerous tissue for improving patient outcomes. Methods: A prospective, open-label, single-center, single dose, exploratory phase II clinical trial (EudraCT 2022-001361-12) to assess the efficacy of the novel uPAR-targeting near-infrared imaging agent, FG001, for intraoperative detection of OSCC and OPSCC. Macroscopic tumor detection was quantified with sensitivity and intraoperative tumor-to-background ratio (TBR). Microscopic tumor-specificity was assessed by analysis of morphological co-localization between tumor tissue, uPAR-expression, and optical signal. Blood samples were collected up to 44 hours post-injection to further characterize the pharmacokinetic profile of the agent. The trial was conducted with close safety monitoring. Results: Sixteen patients undergoing primary surgical resection were systemically administered 36 mg (n = 4), 16 mg (n = 8), or 4 mg (n = 4) of FG001 the evening prior to surgery. Intraoperatively, using a near-infrared imaging system, real-time optical imaging successfully identified all 16 tumors (sensitivity: 100%, mean TBR: 2.99 range: 2.02 - 3.95), and tumor-specificity was confirmed by histology. Clinical neck metastasis was detected with optical imaging. The maximal plasma concentrations were measured after 1 hour, and the half-life of FG001 was 12 hours. No drug-related or serious adverse events were observed. Conclusions: FG001 holds great potential for optical molecular imaging of OSCC and OPSCC. Further trials are warranted to explore FG001 for intraoperative margin delineation and as a decision-making tool.

The role of radiotherapy in intracranial hemangiopericytoma/solitary fibrous tumors : ATurkish Society for Radiation Oncology Central Nervous System Tumors Group Study (TROD 07-008).

Intracranial hemangiopericytomas (HPC) are rare tumors. Radiotherapy (RT) is frequently performed after surgery, depending on tumor size, location, and the type of resection. Moreover, RT is preferred as an effective treatment for local recurrence and metastasis. With this multicenter study, we aimed to investigate the effectiveness of postoperative RT in intracranial HPC patients using modern RT techniques. Patients aged 16years and older who underwent RT for histologically confirmed intracranial HPC were evaluated retrospectively. Forty-four patients from 17institutions were included. Demographic characteristics of the patients, pathological findings, and prognostic factors were documented. The Kaplan-Meier method was used for local control (LC), distant metastasis-free survival (DMFS), progression-free survival (PFS), and overall survival (OS). The interval for survival analyses was calculated according to the end date of RT. Univariate and multivariate analysis methods were used for factors associated with survival and recurrence. Median age was 42years (16-71) and 70% of the patients were male. The most common initial symptoms were pain (47.7%) and vision problems (15.9%). Asupratentorial location was observed in 79.5% of patients. The median maximum tumor dimension was 4.7 (1.6-14) cm. Gross total (GTR) and subtotal resection (STR) were performed in 43.2% and 47.7% of patients, respectively. Adjuvant RT commenced amedian of 6 (2-16) weeks after surgery. Postoperative RT was administered using conventionally fractionated intensity-modulated radiotherapy (IMRT) or stereotactic radiosurgery (SRS). Atotal median dose of 60(38-66) Gy in amedian of 30(19-33) fractions was used for patients treated with IMRT and atotal median dose of 24(12-25) Gy in amedian of 3(1-5) fractions was used for patients treated with SRS. Local recurrence occurred in 9patients and locoregional recurrence in 2patients at amedian of 48months (range 26-143 months) after RT. Reoperation and reirradiation were applied to 5patients, reirradiation to 4patients, and reoperation to 2patients as salvage treatments. Reirradiation was administered at amedian dose of 35 (13.5-54) Gy using amedian of 5 (1-30) fractions. At amedian follow-up of 63 (6-262) months, 5‑year LC was 68.7%, DMFS 87.2%, PFS 60.8%, and OS 95.7%. The presence of residual macroscopic tumor before RT was associated with lower LC (p = 0.01) and shorter PFS (p = 0.04). In the presence of residual tumor before RT, 5‑year LC decreased from 92.9% to 46.7%, while 5‑year PFS decreased from 81.1% to 43.5% compared to patients with GTR. The presence of postoperative tumor was associated with alower LC rate in Cox regression analyzes (p = 0.02). The hazard ratio was 6.2 (1.2-30). However, the effect of residual disease before RT on OS was not statistically significant. Adjuvant radiotherapy is performed in the majority of patients with HPC, especially in cases where GTR cannot be performed. In our study, postoperative macroscopic residual tumor was found to be the only factor affecting LC and PFS in patients undergoing adjuvant RT, but its effect on OS was not shown. This may be due to the effectiveness of reoperation and/or reirradiation in the presence of recurrence after RT.

Liver resection in patients with a history of local ablation for hepatocellular carcinoma has the risk of poor survival and serosal invasion

AbstractAimThe aim was to evaluate the impact of previous local ablation (LA) on long‐term prognoses and tumor histopathological findings following hepatectomy for hepatocellular carcinoma (HCC).MethodsThis retrospective study used data from patients who underwent initial hepatectomy for HCC at Ehime University Hospital between October 2003 and July 2021. Using data from a total of 234 patients, after excluding patients with distant metastasis or macroscopic residual tumors and patients with mixed HCC, a group of 39 patients who underwent post‐ablation liver resection (PALR) was compared with a group of 195 non‐PALR patients with respect to patient characteristics, perioperative data, pathological findings, and outcomes.ResultsNumber of tumors was significantly greater and diameter of tumor was smaller in PALR group than those of non‐PALR group. Both overall survival (OS) and recurrence‐free survival (RFS) were significantly poor in PALR group than those of non‐PALR (5‐year OS 54.1% vs. 66.9%, p = 0.024; 5‐year RFS 24.7% vs. 37.0%, p = 0.019). However, PALR was not selected as independent prognosticator in multivariate analyses. In PALR group, tumor size ≥3 cm was sole independent prognosticator in multivariate analyses. Multivariate analysis showed that PALR [odds ratio (OR), 8.989; 95% confidence interval (CI), 2.807–28.787], alpha‐fetoprotein level >40 ng/mL (OR, 2.923; 95% CI, 1.063–8.035), and des‐γ‐carboxyprothrombin level >170 mAU/mL (OR, 5.164; 95% CI, 1.622–16.438) were independent predictors of pathological serosal invasion.ConclusionsHepatectomy for patients with history of LA for HCC had a risk of serosal invasion and poor survival.

Therapeutic strategies for mobile spine chordoma: en bloc Versus intralesional surgery with adjuvant charged-particle therapy.

The aim of this retrospective study is to analyze the impact of en bloc resection with negative margins versus intralesional resection plus adjuvant hadron-therapy (HT) on local control (LC) and overall survival (OS) in patients with mobile spine chordomas. Mechanical complications incidence as well as risk factors, and outcome differences are investigated as secondary endpoints. 33 patients in a period from January 2013 to December 2021 were enrolled for the final analysis. The inclusion criteria were: lesions located in the mobile spine (C1-L5), age ≥ 15 years, minimum follow-up of 2 years, en bloc or intralesional surgical resection, virgin or recurrent chordomas, with only one previous surgical treatment. No difference was found in terms of LC between the two groups. The presence of pathologic fracture at pre-operative imaging and the presence of macroscopic residual tumor after surgery, independently from its entity, seemed to be associated with an increased risk of LR. No difference was found between planned en bloc and planned intralesional surgery in terms of mechanical complications occurrence. Eight patients (24.24%) had mechanical complications during the follow up period: male sex, presence of pathologic fracture at baseline, a combined surgical approach, the use of carbon fiber-only hardware appeared to be associated with an increased risk of mechanical complications after the primary surgery. En bloc resection, whenever possible, is always to be preferred for its widely recognized potential in LC and OS improvement. However, technology advances in high-dose conformal charged-particle therapy have allowed improvement of local control rates as an adjuvant therapy of intralesional surgery for mobile spine chordoma, with acceptable acute and chronic toxicity.

6955 A Rare Case of Rapidly Enlarging High Grade Follicular-Derived Carcinoma in a Young Patient - Formerly Known as Insular Thyroid Carcinoma with good response to Radioactive iodine ablation- A New Name, Same Aggressive Features

Abstract Disclosure: R. Abdelmasih: None. N. Prasad: None. N. Shah: None. Introduction: Follicular-derived thyroid carcinomas, formerly known as insular thyroid carcinomas, are an albeit rare but highly lethal thyroid carcinoma subtype with an incidence of 1-10% worldwide. It is known for its aggressive nature and comprises the majority of deaths from non-anaplastic follicular thyroid cancers. Case Presentation: A 30-year-old male presented with 2-year history of progressively enlarging painless right neck mass. Physical exam revealed 6x3 cm right well-circumscribed mobile mass not displacing the trachea. Head and neck CT showed 6.5 cm right thyroid mass with level 2A lymph node. Neck Ultrasound showed a 6.4 cm right thyroid nodule. Fine needle aspiration of the mass showed atypia of undetermined significance. Patient returned to clinic 1 year later with progressively enlarging right neck mass, now associated with dysphagia measuring 10 cm in physical exam deviating the trachea to the left. Repeat CT H&N showed 10 cm right thyroid mass with moderate tracheal deviation and US showed 11 cm right heterogenous thyroid mass with regular margins and negative LNs. Patient underwent right thyroid lobectomy with surgical pathology showed 11.4 cm tumor with vascular invasion and no extrathyroidal extension. Pathology showed high grade follicular-derived Thyroid Carcinoma. Patient underwent completion thyroidectomy with benign pathology followed by radioactive iodine ablation 107.8 mCi I131 with successful targeting of residual thyroid tissue and no evidence of iodine avid distant metastasis. Patient has been followed closely for 2 years now with regular US, thyroglobulin level with recurrence. Discussion: Insular thyroid carcinomas are aggressive malignancies predominantly seen in females within the age of 55-65 though cases of young patients and children have been reported. Patients often present with enlarging goiter, dysphagia, and dyspnea however, metastatic disease to lymph nodes, lung and bone has also been reported as primary presentation in 20% of cases. Per literature review, recurrence and mortality rates have very wide range of 36-83% and 9-75% respectively which could be explained by a variety of prognostic factors including Patient age, tumor size, Macroscopic evident extrathyroidal extension, distant metastasis, or tumor necrosis. Often times insular thyroid carcinomas are mistaken for anaplastic carcinoma and thus fine needle aspiration is a helpful diagnostic tool to differentiate insular carcinoma. Pathology typically demonstrates well-defined insulae of thyroglobulin-filled follicles, necrotic foci, and high random mitotic activity. Treatment includes total thyroidectomy followed by high-dose radiotherapy. We Present this case to shed light on such a rare aggressive entity that requires early detection, belligerent management, and close follow-up for promising outcomes. Presentation: 6/3/2024

392. MACHINE LEARNING TO PREDICT LYMPH NODE METASTASIS IN T1 ESOPHAGEAL SQUAMOUS CELL CARCINOMA: A MULTICENTER STUDY

Abstract Background Lymph node metastases (LNM) is a relatively uncommon but possible complication of T1 esophageal squamous cell carcinoma (ESCC). Existing models do poorly when it comes to quantifying this risk. As a branch of artificial intelligence, machine learning (ML) algorithms have developed and become more prominent. Up to now, no individualized ML prediction model aimed at predicting LNM in T1 esophageal squamous cell carcinoma patients is available. This study aimed to develop a machine learning model for LNM in patients with T1 esophageal squamous cell carcinoma. Methods Patients with T1 squamous cell carcinoma treated with surgery between January 2010 and September 2021 from 3 institutions were included. Machine-learning models were developed using data on patients’ age and sex, depth of tumor invasion, tumor size, tumor location, macroscopic tumor type, lymphatic and vascular invasion, and histologic grade. Elastic net regression (ELR), random forest (RF), extreme gradient boosting (XGB), and a combined (ensemble) model of these was generated. Use Area Under Curve (AUC) to evaluate the predictive ability of models. The contribution of each factor was calculated. To meet clinical needs, we designed the model as a user-friendly website. Results 926 and 341 patients were included in the derivation and validation cohorts. The lymph node metastasis rate was 14.8%. The models all exhibited potent discriminating power. The elastic net regression model performed best with externally validated AUC of 0.803 (AUC 0.773 for RF, 0.791 for XGB, 0.799 for ensemble) whereas the NCCN guidelines identified patients with LNM with an AUC of 0.576 and logistic model with an AUC of 0. 670. The most important features were lymphatic and vascular invasion as well as depth of tumor invasion. Conclusions The model created utilizing machine learning approaches had excellent performance estimating the likelihood of LNM in T1 ESCC, which can help patients achieve personalized treatment options.

Pexidartinib Upfront in a Case of Tenosynovial Giant Cell Tumor: Proof of Concept for a Treatment Paradigm Shift.

Tenosynovial giant cell tumor (TGCT) is a rare, locally aggressive tumor of the joints, bursa, and tendon sheath that can cause considerable pain and substantial morbidity. Although surgery is the primary treatment for patients with TGCT, surgical resection is associated with high rates of recurrence, particularly for patients with diffuse TGCT. Pexidartinib, a colony-stimulating factor1 receptor inhibitor, is approved by the US Food and Drug Administration for the treatment of adult patients with symptomatic TGCT associated with severe morbidity or functional limitations and not amenable to improvement with surgery. A 32-year-old man presented with intra-articular diffuse TGCT with pain and received noncurative treatment for 5years (2014-2019). In 2019, the patient was found to have extensive disease accompanied by pain and limited range of motion. The patient's case was presented to a sarcoma multidisciplinary tumor board, who determined that surgery would cause significant morbidity and macroscopic residual tumor. As a result of the extent of disease, young age, and otherwise good health, treatment with pexidartinib was started through a compassionate use program at 800mg/day. After dose reductions to pexidartinib at 400mg/day and then 200mg/day as a result of creatine phosphokinase elevations, the patient achieved a complete response after 2years of treatment; pain was reduced and mobility was restored. The patient reported no side effects related to pexidartinib treatment. Treatment was stopped in 2022 for future family planning. After pexidartinib therapy was interrupted, the patient's wife had a successful pregnancy and delivery; however, the disease showed a slow but constant clinical deterioration, with a reduction in the range of movement of the affected knee and an apparent increase in widespread TGCT nodules. Our case is unique because it provides support for pexidartinib use as upfront therapy for TGCT, instead of surgery, in selected cases.

Evaluation of the efficacy and safety of toceranib phosphate in cats with macroscopic mammary adenocarcinoma.

Mammary tumours in cats are biologically aggressive. The standard of care relies upon wide surgical resection. Chemotherapy has been described in the macroscopic disease setting; however, limited efficacy has been shown. The aim of this study was to assess the efficacy of toceranib phosphate in macroscopic feline mammary tumours (FMTs). A total of 17 cats with cytologically or histopathologically confirmed mammary adenocarcinoma (gross disease) were prospectively enrolled. Toceranib phosphate was administered at a median dose of 2.77 mg/kg (range 2.3-3.2) PO q48 h. No corticosteroids or non-steroidal anti-inflammatory drugs (NSAIDs) were administered. Toxicity was graded according to Veterinary Cooperative Oncology Group-Common Terminology Criteria for Adverse Events (VCOG-CTCAE) v1.1 criteria. The response was assessed after 1 month, following Response Evaluation Criteria In Solid Tumours (RECIST) criteria. Toxicity was observed in eight cats, with most instances being grade 1 or 2, which were managed with supportive care. Only one cat experienced grade 3 toxicity (anorexia), which resolved after a dose reduction. Clinical benefit was seen in 12 (64.7%) cats and an objective response was seen in six (35.2%) cats. One cat experienced complete response, five had partial response, six had stable disease and five had progressive disease. One cat showed distant progression (malignant pleural effusion) despite continued partial remission of the primary tumour. The median progression-free survival and median overall survival time were 91 days (range 30-158) and 145 days (range 31-234), respectively. Toceranib phosphate showed clinical benefit and a good safety profile in advanced or recurrent FMTs, offering a new alternative in the treatment of this disease; however, further prospective and randomised studies are required to further assess its efficacy. Interestingly, one cat developed distant metastases while the primary tumour showed partial response, suggesting that primary tumour and metastatic disease may not sustain the same sensitivity to toceranib.

Prediction of nonresectability using the updated Predictive Index value model assessed by imaging and surgery in tubo-ovarian cancer: a prospective multicenter ISAAC study

BackgroundA laparoscopy-based scoring system was developed by Fagotti et al (Fagotti or Predictive Index Value (PIV)score) based on the intraoperative presence or absence of carcinomatosis on predefined sites. Later, the authors updated the PIV score calculated only in the absence of one or both absolute criteria of non-resectability (mesenteric retraction and miliary carcinomatosis of the small bowel) (updated PIV model). ObjectiveThe aim was to demonstrate the non-inferiority of ultrasound to other imaging methods (contrast enhanced computed tomography (CT) and whole-body diffusion-weighted (WB DWI)/MRI) in predicting non-resectable tumor (defined as residual disease>1 cm) using the updated PIV model in patients with tubo-ovarian cancer. The agreement between imaging and intraoperative findings as a reference was also calculated. Study designThis was a European prospective multicenter observational study. We included patients with suspected tubo-ovarian carcinoma who underwent preoperative staging and prediction of non-resectability at ultrasound, CT, WB-DWI/MRI and surgical exploration. The predictors of non-resectability were suspicious mesenteric retraction and/or miliary carcinomatosis of the small bowel or if absent, a PIV>8 (updated PIV model). The PIV score ranges from 0 to 12 according to the presence of disease in six predefined intra-abdominal sites (great omentum, liver surface, lesser omentum/stomach/spleen, parietal peritoneum, diaphragms, bowel serosa/mesentery). The reference standard was surgical outcome, in terms of residual disease>1 cm, assessed by laparoscopy and/or laparotomy. The area under the receiver operating characteristic curve (AUC) to assess the performance of the methods in predicting non-resectability was reported. Concordance between index tests at detection of disease at six predefined sites and intraoperative exploration as reference standard was also calculated using Cohen’s kappa. ResultsThe study was between 2018 and 2022 in five European gynecological oncology centers. Data from 242 patients having both mandatory index tests (ultrasound and CT) were analyzed. 145/242 (59.9%) patients had no macroscopic residual tumor after surgery (R0) (5/145 laparoscopy and 140/145 laparotomy) and 17/242 (7.0%) had residual tumor ≤1cm (R1) (laparotomy). In 80/242 patients (33.1%), the residual tumor was >1 cm (R2), 30 of them underwent laparotomy and maximum surgery was carried out and 50/80 underwent laparoscopy and cytoreduction was not feasible in all of them.After excluding 18/242 (7.4%) patients operated on but not eligible for extensive surgery, the predictive performance of three imaging methods was analyzed in 167 women. The AUCs of all methods in discriminating between resectable and non-resectable tumor was 0.80 for ultrasound, 0.76 for CT, 0.71 for WB-DWI/MRI and 0.90 for surgical exploration. Ultrasound had the highest agreement (Cohen’s kappa ranging from 0.59 to 0.79) compared to CT and WB-DWI/MRI to assess all parameters included in the updated PIV model. ConclusionsUltrasound showed non-inferiority to CT and to WB-DWI/MRI in discriminating between resectable and non-resectable tumor using the updated PIV model. Ultrasound had the best agreement between imaging and intraoperative findings in the assessment of parameters included in the updated PIV model. Ultrasound is an acceptable method to assess abdominal disease and predict non-resectability in patients with tubo-ovarian cancer in the hands of specially trained ultrasound examiners.

Basic cell carcinoma of the vulva. Case report and literature review

Background: Vulvar carcinoma is rare, 4% of gynecological cancer worldwide and basal cell carcinoma of these represents 2 to 3%; Its diagnosis is delayed due to carelessness of the patient and doctor. Objective: To present a clinical case of basal cell carcinoma of the vulva and review of the literature. Clinical case: A 58-year-old patient, without comorbidities or risk factors, who presented a nodule in the upper third of the right labia majora; Excisional biopsy was performed with margins free of macroscopic tumor, basal cell carcinoma was reported. Methodology: A narrative review is carried out from 2014 to 2021 in PubMed, scholaris, SciELO Google scholar and books, finding 27 articles and only 20 were included for reliability, impact factor. Results: Vulvar cancer represents 4% of gynecological cancer worldwide. 0.4% of all basal cell carcinomas occur in the genital region, and in the vulva it represents 2 to 4% of all vulvar cancers. Basal cell carcinoma of the vulva most commonly presents as a solitary pink or pigmented papule or plaque on the labia majora; bilateral and multifocal lesions may occur. Basal cell carcinoma of the vulva is an extremely rare tumor that rarely metastasizes or spreads. . Primary treatment should consist of wide local excision and continuous monitoring. Conclusion: Any suspicious lesion of the vulva must be biopsied to reach a timely diagnosis and treatment, the rarity of these lesions and the lack of care on the part of the patient and the negligence of the doctor not to perform an examination of the vulva, the lesions progress until symptoms occur or are discovered during medical examination, vulvar cancer is suspected, radical excisional biopsy is the correct therapeutic approach.

The Value of PET/CT in Particle Therapy Planning of Various Tumors with SSTR2 Receptor Expression: Comparative Interobserver Study.

The overexpression of somatostatin receptor type 2 (SSTR2) is a property of various tumor types. Hybrid imaging utilizing [68Ga]1,4,7,10-tetraazacyclododecane-1,4,7,10-tetra-acetic acid (DOTA) may improve the differentiation between tumor and healthy tissue. We conducted an experimental study on 47 anonymized patient cases including 30 meningiomas, 12 PitNET and 5 SBPGL. Four independent observers were instructed to contour the macroscopic tumor volume on planning MRI and then reassess their volumes with the additional information from DOTA-PET/CT. The conformity between observers and reference volumes was assessed. In total, 46 cases (97.9%) were DOTA-avid and included in the final analysis. In eight cases, PET/CT additional tumor volume was identified that was not detected by MRI; these PET/CT findings were potentially critical for the treatment plan in four cases. For meningiomas, the interobserver and observer to reference volume conformity indices were higher with PET/CT. For PitNET, the volumes had higher conformity between observers with MRI. With regard to SBGDL, no significant trend towards conformity with the addition of PET/CT information was observed. DOTA PET/CT supports accurate tumor recognition in meningioma and PitNET and is recommended in SSTR2-expressing tumors planned for treatment with highly conformal radiation.

Radiotherapy for Canine Apocrine Gland Anal Sac Adenocarcinoma: Survival Outcomes and Side Effects of a Palliative Treatment Protocol of 20 Gy in Five Consecutive Fractions.

This research aims to evaluate the outcomes of a radiotherapy protocol, consisting of five fractions of 4 Gy each, resulting in a total dose of 20 Gy for apocrine gland anal sac tumors and local lymph nodes in canines. This protocol was assessed as a palliative treatment for macroscopic tumors alone, or in combination with additional therapies under different scenarios. Medical records from fifty canine patients met the inclusion criteria and were divided into different treatment groups: radiotherapy alone (n = 22, 44%), radiotherapy with chemotherapy or targeted therapy with toceranib (n = 18, 36%), surgery with radiotherapy (n = 5, 10%), and surgery with radiotherapy and chemotherapy or targeted therapy with toceranib (n = 5, 10%). Patients who received radiotherapy alone had a median survival time of 384 days (95% CI 198-569) and 628 days (95% CI 579-676) for RT + additional therapies. The median time to progression for patients with radiotherapy alone was 337 days (95% CI 282-391 days), and 402 days (95% CI 286-517 days) for radiotherapy plus additional treatments. Acute side effects were mild, with the majority having diarrhea (61%), and only one patient developed grade III late effects VRTOG v2 classification; however, this happened 22 months after the first radiotherapy protocol after re-irradiation. The results demonstrate that radiotherapy alone under this protocol provided a comparable median time to progression vs. radiotherapy plus additional treatments while maintaining acceptable side effects. The combination of this protocol with other treatment modalities offers attractive results for local disease control and survival while maintaining acceptable toxicities. Overall, these findings contribute to the growing evidence supporting the role of radiotherapy in managing apocrine gland anal sac adenocarcinoma in dogs.

Muscle-invasive bladder cancer in elderly and frail people: Is hypofractionated radiotherapy a feasible approach when no other local options are available?

The study aims to report the feasibility and safety of palliative hypofractionated radiotherapy targeting macroscopic bladder tumors in a monocentric cohort of frail and elderly bladder cancer patients not eligible for curative treatments. Patients who underwent hypofractionated radiotherapy to the gross disease or to the tumor bed after transurethral resection of bladder tumor from 2017 to 2021 at the European Institute of Oncology IRCCS, were retrospectively considered. Schedules of treatment were 30 and 25 Gy in 5 fractions (both every other day, and consecutive days). Treatment response was evaluated with radiological investigation and/or cystoscopy. Toxicity assessment was carried out according to RTOG/EORTC v2.0 criteria. A total of 16 patients were included in the study, of these 11 received hypofractionated radiotherapy on the macroscopic target volume and five on the tumor bed after transurethral resection of bladder tumor. No grade (G) >2 acute toxicities were described after treatment for both groups. Only one patient in the group receiving radiotherapy on the macroscopic disease reported G4 GU late toxicity. Ten patients had available follow-up status (median FU time 18 months), of them six had complete response, one had stable disease, and three had progression of disease. The overall response rate and disease control rate were 60% and 70%, respectively. Our preliminary data demonstrate that palliative hypofractionated radiotherapy for bladder cancer in a frail and elderly population is technically feasible, with an acceptable toxicity profile. These outcomes emphasize the potential of this approach in a non-radical setting and could help to provide more solid indications in this underrepresented setting of patients.

Radiologic tumor border can further stratify prognosis in patients with pancreatic neuroendocrine tumor

Background and objectivesPancreatic neuroendocrine tumor (PanNET), although rare in incidence, is increasing in recent years. Several clinicopathologic and molecular factors have been suggested for patient stratification due to the extensive heterogeneity of PanNETs. We aimed to discover the prognostic role of assessing the tumor border of PanNETs with pre-operative computed tomography (CT) images and correlate them with other clinicopathologic factors. MethodsThe radiologic, macroscopic, and microscopic tumor border of 183 surgically resected PanNET cases was evaluated using preoperative CT images (well defined vs. poorly defined), gross images (expansile vs. infiltrative), and hematoxylin and eosin-stained slides (pushing vs. infiltrative). The clinicopathologic and prognostic significance of the tumor border status was compared with other clinicopathologic factors. ResultsA poorly defined radiologic tumor border was observed in 65 PanNET cases (35.5 %), and were more frequent in male patients (P = 0.031), and tumor with larger size, infiltrative macroscopic growth pattern, infiltrative microscopic tumor border, higher tumor grade, higher pT category, lymph node metastasis, lymphovascular and perineural invasions (all, P < 0.001). Patients with PanNET with a poorly defined radiologic tumor border had significantly worse overall survival (OS) and recurrence-free survival (RFS; both, P < 0.001). Multivariable analysis revealed that PanNET with a poorly defined radiologic border is an independent poor prognostic factor for both OS (P = 0.049) and RFS (P = 0.027). ConclusionPre-operative CT-based tumor border evaluation can provide additional information regarding survival and recurrence in patients with PanNET.

The role of Piezo1 mechanotransduction in high-grade serous ovarian cancer: Insights from an in vitro model of collective detachment.

Slowing peritoneal spread in high-grade serous ovarian cancer (HGSOC) would improve patient prognosis and quality of life. HGSOC spreads when single cells and spheroids detach, float through the peritoneal fluid and take over new sites, with spheroids thought to be more aggressive than single cells. Using our in vitro model of spheroid collective detachment, we determine that increased substrate stiffness led to the detachment of more spheroids. We identified a mechanism where Piezo1 activity increased MMP-1/MMP-10, decreased collagen I and fibronectin, and increased spheroid detachment. Piezo1 expression was confirmed in omental masses from patients with stage III/IV HGSOC. Using OV90 and CRISPR-modified PIEZO1-/- OV90 in a mouse xenograft model, we determined that while both genotypes efficiently took over the omentum, loss of Piezo1 significantly decreased ascitic volume, tumor spheroids in the ascites, and the number of macroscopic tumors in the mesentery. These results support that slowing collective detachment may benefit patients and identify Piezo1 as a potential therapeutic target.

Plasma extracellular vesicles in meningioma patients following radiotherapy as liquid biopsy- a prospective explorative biomarker study (ARO 2023-05/AG-NRO-07)

BackgroundWhile surgical resection remains the primary treatment approach for symptomatic or growing meningiomas, radiotherapy represents an auspicious alternative in patients with meningiomas not safely amenable to surgery. Biopsies are often omitted in light of potential postoperative neurological deficits, resulting in a lack of histological grading and (molecular) risk stratification. In this prospective explorative biomarker study, extracellular vesicles in the bloodstream will be investigated in patients with macroscopic meningiomas to identify a biomarker for molecular risk stratification and disease monitoring.MethodsIn total, 60 patients with meningiomas and an indication of radiotherapy (RT) and macroscopic tumor on the planning MRI will be enrolled. Blood samples will be obtained before the start, during, and after radiotherapy, as well as during clinical follow-up every 6 months. Extracellular vesicles will be isolated from the blood samples, quantified and correlated with the clinical treatment response or progression. Further, nanopore sequencing-based DNA methylation profiles of plasma EV-DNA will be generated for methylation-based meningioma classification.DiscussionThis study will explore the dynamic of plasma EVs in meningioma patients under/after radiotherapy, with the objective of identifying potential biomarkers of (early) tumor progression. DNA methylation profiling of plasma EVs in meningioma patients may enable molecular risk stratification, facilitating a molecularly-guided target volume delineation and adjusted dose prescription during RT treatment planning.

Robustness of radiomic features in healthy abdominal parenchyma of patients with repeated examinations on dual-layer dual-energy CT

ObjectivesRobustness of radiomic features in physiological tissue is an important prerequisite for quantitative analysis of tumor biology and response assessment. In contrast to previous studies which focused on different tumors with mostly short scan-re-scan intervals, this study aimed to evaluate the robustness of radiomic features in cancer-free patients and over a clinically encountered inter-scan interval. Materials and methodsPatients without visible tumor burden who underwent at least two portal-venous phase dual energy CT examinations of the abdomen between May 2016 and January 2020 were included, while macroscopic tumor burden was excluded based upon follow-up imaging for all patients (≥3 months). Further, patients were excluded if no follow-up imaging was available, or if the CT protocol showed deviations between repeated examinations. Circular regions of interest were placed and proofread by two board-certified radiologists (4 years and 5 years experience) within the liver (segments 3 and 6), the psoas muscle (left and right), the pancreatic head, and the spleen to obtain radiomic features from normal-appearing organ parenchyma using PyRadiomics. Radiomic feature robustness was tested using the concordance correlation coefficient with a threshold of 0.75 considered indicative for deeming a feature robust. ResultsIn total, 160 patients with 480 repeated abdominal CT examinations (range: 2–4 per patient) were retrospectively included in this single-center, IRB-approved study. Considering all organs and feature categories, only 4.58 % (25/546) of all features were robust with the highest rate being found in the first order feature category (20.37 %, 22/108). Other feature categories (grey level co-occurrence matrix, grey level dependence matrix, grey level run length matrix, grey level size zone matrix, and neighborhood gray-tone difference matrix) yielded an overall low percentage of robust features (range: 0.00 %-1.19 %). A subgroup analysis revealed the reconstructed field of view and the X-ray tube current as determinants of feature robustness (significant differences in subgroups for all organs, p < 0.001) as well as the size of the region of interest (no significant difference for the pancreatic head with p = 0.135, significant difference with p < 0.001 for all other organs). ConclusionRadiomic feature robustness obtained from cancer-free subjects with repeated examinations using a consistent protocol and CT scanner was limited, with first order features yielding the highest proportion of robust features.

A Hepatocellular Cancer Patient-derived Organoid Xenograft Model to Investigate Impact of Liver Regeneration on Tumor Growth.

Recurrence poses a notable challenge after hepatocellular carcinoma (HCC) treatment, impacting more than 70% of patients who undergo surgical resection. Recurrence stems from undetected micro-metastasis or de novo cancer, potentially triggered by postsurgical liver regeneration. Prior research employed HCC cell lines in orthotopic models to study the impact of liver regeneration, but their limited validity prompted the need for a more representative model. Here, we introduce a novel approach utilizing patient-derived HCC organoids to investigate the influence of liver regeneration on HCC. Patient tumor tissues are processed to create tumor organoids, embedded in a three-dimensional basement membrane matrix, and cultured in a liver-specific medium. One million organoids are injected into the right superior lobe (RSL) of immunodeficient mice, confirming macroscopic tumor growth through sonography. The intervention group undergoes resection of the left lateral lobe (LLL) (30% of total liver volume) or additionally, the middle lobe (ML) (65% of total liver volume) to induce liver regeneration within the tumor site. The control group experiences re-laparotomy without liver tissue resection. After 2 weeks, both groups undergo tumor and normal tissue explantation. In conclusion, this patient-derived HCC organoid model offers a robust platform to investigate the impact of liver regeneration post-cancer resection. Its multi-cellular composition, genetic diversity, and prolonged culture capabilities make it an invaluable tool for studying HCC recurrence mechanisms and potential interventions.

Canine primary liver tumors treated with stereotactic body radiation therapy: A case series.

Stereotactic body radiation therapy (SBRT) is an increasingly used alternative treatment option for nonresectable hepatocellular carcinoma (HCC) in people. Comparatively, the publication of SBRT of dogs with HCC is limited. The objective of this retrospective, descriptive case series was to evaluate the clinical outcomes and toxicity data of SBRT in dogs with HCC and imaging-documented primary liver tumors using volumetric-modulated arc therapy delivery at two private institutions. Medical records of 14 dogs treated between 2018 and 2023 were reviewed. All dogs had macroscopic tumors, and 9 of 14 dogs had HCC diagnoses confirmed on cytology or histopathology. The median longest tumor diameter was 5.5cm. The median percentage of planning target volume relative to liver volume was 27.1%. Most dogs were treated with three daily fractions of 7-7.5Gy. All dogs completed their radiotherapy protocols. Three of nine HCC dogs experienced partial responses and clinical improvement. Five of nine HCC dogs had stable disease. Overall median survival time was 164 days for nine HCC dogs (range: 93-706 days). One late grade 5 liver and two late grade 3 kidney side effects were reported. One dog received repeated SBRT to the same HCC treatment field, and one dog had two courses of SBRT to bifocal HCC treatment fields, both with no more than grade 2 acute and chronic toxicities.