Local Disease Control Research Articles

External Beam Radiotherapy Interdigitated with High Dose Rate(HDR) Intracavitary Brachytherapy versus External Beam Radiotherapy followed by Sequential HDR Intracavitary Brachytherapy for Locally Advanced Carcinoma Cervix-Randomized Control Study.

In cervical cancer treatment, overall treatment time (OTT) is an important prognostic factor. This study compares the clinical outcomes when High-Dose-Rate Intracavitary-Brachytherapy(HDR-ICRT) is interdigitated with external beam radiotherapy(EBRT) versus sequential HDR-ICRT after EBRT in the treatment of locally advanced carcinoma cervix. Histologically confirmed carcinoma cervix patients [FIGO Stage IIB-IVA (except IIIC-2)] were included and randomized into two groups. The study group received EBRT 50Gy in 25 fractions with interdigitated HDR-ICRT 7Gy per fraction weekly for three fractions starting after completion of 3 weeks of EBRT or as soon as cervical os became negotiable thereafter. Patients in the control group received EBRT 50Gy in 25 fractions with sequential HDR-ICRT 7Gy per fraction weekly for three fractions starting one week after completion of EBRT. All patients were regularly followed up during and after radiotherapy for local toxicity and disease control. This study enrolled 102 patients; 51 in each arm. Median OTT in study and control arm were 46 and 60 days, respectively. Median follow-up duration was 24 months (two years). Loco-regional control after two years of follow-up was 84.31 % and 72.54% of patients in study arm control arm respectively (p-value 0.148). Two (3.92%) patients from study arm and eight (15.68%) from control arm had residual disease. Two patients in study arm and one from control arm had local recurrence. Two patients from study arm three patients from control arm developed distant metastases. RTOG mucosal grade III acute mucosal toxicity in either arm. Cervical-os negotiability was limiting factor for interdigitated HDR-ICRT. Interdigitated HDR-ICRT with EBRT may give local control with manageable toxicities as compared to sequential HDR-ICRT, with the advantage of significant reduction in OTT.<br />.

Long-Term Outcomes Associated with Different High-Dose-Rate Brachytherapy Dose Regimens for Favorable and Unfavorable Intermediate Risk Prostate Cancer.

To present long-term efficacy outcomes of prostate high-dose-rate (HDR) brachytherapy monotherapy using 38 Gy in 4 fractions, 24 Gy in 2 fractions, and 27 Gy in 2 fractions for men with favorable and unfavorable intermediate risk prostate cancer. Patients treated with HDR brachytherapy monotherapy for NCCN favorable (FIR) or unfavorable (UIR) intermediate risk prostate cancer from 1999-2020 were identified in a prospectively maintained, single institution database. Patients with less than two years of follow-up and those treated with single fraction HDR brachytherapy were excluded. Biochemical failure was determined using Phoenix criteria. 10-year biochemical control (BC), local control (LC), and distant metastasis (DM) rates were estimated using the Kaplan-Meier method. Two hundred sixty-seven patients were included. One hundred eighty-nine had FIR and 78 had UIR prostate cancer, with median follow-up of 9.6 years and 7.2 years, respectively. Of the 189 patients with FIR prostate cancer, 59 (31.2%) received 38 Gy in 4 fractions, 26 (13.7%) received 24 Gy in 2 fractions, and 104 (55.0%) received 27 Gy in 2 fractions. Of the 78 patients with UIR prostate cancer, 20 (25.6%) received 38 Gy in 4 fractions, 11 (14.1%) received 24 Gy in 2 fractions, and 47 (60.2%) received 27 Gy in 2 fractions. Date ranges of treatment for the respective fractionation schedules were 1999-2010, 2007-2016, and 2009-2020. Upfront androgen deprivation therapy (ADT) was given to 12 (6.3%) patients with FIR and 10 (12.8%) patients with UIR. 10-year rates of BC for FIR and UIR patients were 90.1% and 78.8% (p = 0.004), respectively. 10-year rates of LC were 92.4% and 85.0% (p = 0.06), respectively. 10-year rates of DM were 1.9% and 4.7% (p = 0.12), respectively. For FIR patients, 10-year BC rates were 96.2% for patients receiving 38 Gy in 4 fractions vs. 86.3% (p = 0.07) for those treated with the 2-fraction regimens, while 10-year LC rates were 97.9% and 89.0% (p = 0.049), respectively. Within the UIR subset, the 10-year BC rates for patients receiving 38 Gy in 4 fractions and patients receiving treatment in 2 fractions were 95.0% and 70.6% (p = 0.038). 10-year LC rates were 100% and 77.8% (p = 0.045), respectively. 10-year BC rates by treatment schedule are shown in the table below. HDR brachytherapy monotherapy results in excellent long-term local control for intermediate risk prostate cancer. Improvements in biochemical and local disease control for patients treated with 38 Gy in 4 fractions warrants consideration of prospective study of optimal treatment dosing regimens.

Favorable Toxicity and Local Control with Ultrahypofractionated Radiation Therapy (UH-RT) for Melanoma of the Lower Genital Tract (LGT)

To report our experience using UH-RT +/- immunotherapy (IO) in women with melanoma of the LGT. We retrospectively identified 23 patients who received UH-RT to primary tumor for vulvovaginal melanoma from 2012 to 2022. Median age was 69 years (IQR: 62-76). Stage included localized, node positive, or metastatic. 18 (78%) had tumors involving the vagina/cervix and 5 (22%) had vulvar tumors. 6 patients had c-KIT mutations; 13 patients were wild-type; 4 patients were unknown. 12 (52%) were treated at initial presentation (cohort A) and 11 (48%) at local progression/recurrence following prior therapy (cohort B). In cohort A, most (n = 11) received concurrent IO. In cohort B, 3 recurred after surgery alone, 4 after systemic therapy alone and 4 after surgery and systemic therapy. RT consisted of 6 Gy x 6 (n = 11), 6 Gy x 5 (n = 10) and 5 Gy x 5-6 (n = 2) delivered to the primary tumor + 0.5 cm margin. Patients initiated IO either ≥3 months preRT (n = 8), concurrent with RT (n = 12) or ≥3 months following RT (n = 2). 1 patient in cohort B did not receive IO. Toxicity was graded using CTCAE v 5. Overall survival (OS) was measured from end of RT. Cumulative incidence of local progression was measured from end of RT. Kaplan-Meier method and Cox regression were used for survival analyses. Landmark method was used for timing of IO. Median follow-up as determined by reverse Kaplan-Meier method was 60 months (95% CI: 37-N/A). Overall incidence of acute/late grade 2+ toxicity for the entire cohort was 34%. Grade 2 acute toxicity included: dermatitis (n = 3), urinary (n = 2), vaginitis (n = 2) and diarrhea (n = 1). 3 patients experienced grade 3 acute dermatitis. 1 patient experienced late grade 2 vaginitis. No grade 3 or 4 toxicity was noted. No significant differences in toxicity were noted between RT regimens. Local disease control was achieved in 61% of patients. Local only, local and distant, and distant-only progression were seen in 17%, 22%, and 30% of patients respectively. 2-year cumulative incidence of local progression was 33% for the whole cohort, 28% for cohort A, and 36% for cohort B (p = 0.4). On UVA, factors associated with local progression were vulvar disease (p = 0.02) and c-KIT mutation (p = 0.011). No significant difference in local control was noted based on biologic effective dose (BED10 < = 48Gy vs >48Gy) (p = 0.06). Median OS for entire cohort, cohort A, and cohort B were 46, 72, and 30 months, respectively. 2-year survival (95% CI) was 67% (50%-91%), 73% (51%-100%), and 64% (41%-99%) respectively. On UVA, non-local disease at time of RT (p = 0.016) and receipt of IO ≥3 months prior to RT (p = 0.030) had worse OS. UH-RT+/- IO for melanoma of the LGT is well-tolerated with local disease control achieved in 61% of patients. Vulvar primary and c-Kit mutations were associated with worse local control. Additional follow-up may be necessary to determine the value of dose escalation.

Patterns of Locoregional Pancreatic Cancer Recurrence after Total Neoadjuvant Therapy and Implications on Optimal Neoadjuvant Radiation Treatment Volumes

Neoadjuvant treatment for patients with localized pancreatic adenocarcinoma (PDAC) has improved survival duration. As survival increases, local disease control becomes even more important. We sought to understand the patterns of locoregional recurrence following total neoadjuvant therapy (TNT) and determine the impact of treatment volumes on recurrence. Patients with PDAC managed with neoadjuvant chemotherapy and chemoradiation (TNT) followed by surgery who developed an isolated locoregional or simultaneously locoregional and distant recurrence were identified. Locoregional recurrences were individually contoured utilizing commercially available software. When available, original neoadjuvant dose distributions were registered to the scans on which the locoregional recurrences were contoured. Recurrences where then classified as in-field (> 95% of prescription dose), marginal (50-95% of prescription dose), or out of field (< 50% of prescription dose). Target volumes were created using four commonly utilized PDAC contouring guidelines to characterize the relationship of the local recurrence to the RT dose distribution. Of 474 patients treated with TNT and surgery, 80 (17%) patients developed a locoregional recurrence with or without distant recurrence, visible on diagnostic imaging. Of the 80 patients, 56 (70%) had tumors in the pancreatic head; 46 (57.5%) were borderline resectable, 23 (28.8%) locally advanced, and 11 (13.6%) resectable. The most common initial neoadjuvant therapies were FOLFIRINOX (57.5%) and gemcitabine/nab-paclitaxel (18.8%). Chemoradiation included concurrent gemcitabine (47.5%) or 5-fluorouracil (26.3%). RT dose distributions were available for 38 patients; 22 (57.9%) had in-field failures, 9 (23.7%) marginal failures, and 7 (18.4%) out of field failures. Each published contouring atlas covered a relatively low percentage of recurrences, which are summarized in Table 1. Regions at particularly high likelihood of recurrence that were under covered on existing atlases included: aortic-diaphragmic junction, retro-pancreatic duodenal nodal basin, and the region to the right of the superior mesenteric artery (SMA). We present the largest series (to our knowledge) of mapped locoregional recurrences for patients being treated with TNT in PDAC. These recurrences differ substantially from established atlases and highlight anatomical regions of highest priority for RT coverage. A novel visual contouring volume highlighting these regions will be presented which will strive to advance the use of RT in the TNT setting.

Translated article] Vertebral metastases. En bloc treatment

En bloc resection of vertebral metastases has been the subject of study in medical literature due to its impact on patients’ quality of life and effectiveness in local disease control. This bibliographic analysis examines the findings and perspectives of published studies concerning en bloc resection of oligometastases in the spine. The technique, which involves the complete removal of the tumour along with a portion of the surrounding bone, has been shown to improve local tumour control, reduce recurrence, and potentially prolong patient survival compared to conventional decompression and stabilisation techniques. However, en bloc resection also presents risks and complications, such as surgical morbidity and extended recovery time. Appropriate patient selection, preoperative planning, and a multidisciplinary approach are essential to optimise outcomes. As new techniques and advances in adjuvant treatment develop, en bloc resection of oligometastases in the spine remains an area of interest in oncological research.

Multi-Disciplinary Management of Hidradenocarcinoma

Hidradenocarcinoma makes up 6% of eccrine malignancies, and is an uncommon eccrine sweat gland tumour. The etiology is due to genetic alterations and transformation from an existing lesion or hidradenoma. It typically affects the face and scalp, although it can also cause nodal involvement and show up on the trunk, abdomen, or groin. Due to its similarities to other skin tumours, it is challenging to diagnose histopathologically. Therefore, immunohistochemical markers, such as p53, Ki-67, keratin AE1/AE3, and cytokeratin 5/6, are crucial for the diagnoses. There are no prospective randomized trials available to direct treatment of hidradenocarcinoma. A key component of therapy is early diagnoses and case discussion in multidisciplinary tumor board. Wide local excision with clear margins is the mainstay of treatment. Adjuvant treatment like chemo radiation therapy is incorporated if nodal disease or positive margins are present. Recurrences are treated by re-excision followed by adjuvant radiation therapy. Adjuvant hormonal therapy depends on the receptor status of the disease. These tumors have a 50% recurrence rate and up to 60% of the time they metastasize to the brain, bone, lung, liver, mediastinum, or peritoneum in a two-year period. The overall five year survival rate is around 30%. Keeping in view the aggressive course of this disease, research based clinically evident new treatment strategies are the need of time to optimize overall survival and local disease control. Keywords: Sweat gland tumors, Adnexal tumors, Hidradenocarcinoma, Adjuvant therapy, Multidisciplinary team, Radiation therapy.

Clinical and dosimetric outcomes of image-guided, dose-painted radiotherapy in muscle invasive bladder cancer

Purpose/ObjectiveDefinitive radiotherapy (RT) is an alternative to radical cystectomy for select patients with muscle invasive bladder cancer (MIBC); however, there is limited data on dose-painted RT approaches. We report the clinical and dosimetric outcomes of a cohort of MIBC patients treated with dose-painted RT.Material/MethodsThis was a single institution retrospective study of cT2-4N0M0 MIBC patients treated with external beam radiotherapy (EBRT) to the bladder, and sequential or concomitant boost to the tumor bed. The target delineation was guided by either intravesical injection of Lipiodol or through fusion of the pre-treatment imaging. The majority were treated with daily image-guidance. Kaplan-Meier was used to characterize overall survival (OS) and progression-free survival (PFS). Cumulative incidence function (CIF) was used to estimate local (intravesical) recurrence (LR), regional recurrence (RR) and distant metastasis (DM). Univariable and multivariable cause-specific hazard model was used to assess factors associated with LR and OS.Results117 patients were analyzed. The median age was 73 years (range 43, 95). The median EQD2 to the boost volume was 66 Gy (range 52.1, 70). Lipiodol injection was used in 64 patients (55%), all treated with IMRT/VMAT. 95 (81%) received concurrent chemotherapy, of whom, 44 (38%) received neoadjuvant chemotherapy. The median follow-up was 37 months (IQR 16.2, 83.3). At 5-year, OS and PFS were 79% (95% CI 70.5–89.2) and 46% (95% CI 36.5–57.5). Forty-five patients had bladder relapse, of which 30 patients (67%) were at site of the tumor bed. Nine patients underwent salvage-cystectomy. Late high-grade (G3-G4) genitourinary and gastrointestinal toxicity were 3% and 1%.ConclusionPartial boost RT in MIBC is associated with good local disease control and high rates of cystectomy free survival. We observed a pattern of predominantly LR in the tumor bed, supporting the use of a dose-painted approach/de-escalation strategy to the uninvolved bladder. Prospective trials are required to compare oncological and toxicity outcomes between dose-painted and homogeneous bladder RT techniques.

Abstract PO-099: Short-term outcomes of an extended endoscopic endonasal resection of a clival giant cell tumor with adjuvant RANK-L inhibitor therapy: Case report

Abstract Background Clival giant cell tumors (GiCT) are rare neoplasms that commonly target the epiphysis. Recently, skull base GiCTs have been reported, predominantly in the sphenoid and temporal bones. Although typically benign, GiCTs of the skull-base can cause neurologic deficits due to compression of cranial nerves or intracranial contents. The efficacy of adjuvant chemotherapy in treating GiCTs is not known. One potential treatment option neoplastic mononuclear stromal cells in GiCTs express NF-κB ligands (RANK-L), which can be therapeutically targeted with Denosumab, a monoclonal antibody against RANK-L. Here, we describe the case of a GiCT invasive to the clivus, an extended endoscopic endonasal resection of the tumor, and management of the lesion with Denosumab. Methods A retrospective chart review was performed on the patient of interest. Magnetic resonance imaging (MRI) and computed tomography (CT) scans were used to assess disease growth and response to surgical and therapeutic intervention. Case presentation A previously healthy seventeen-year-old female presented with headaches and numbness of the left V2 and V3. A diagnosis of a clival giant cell tumor was confirmed with strict pathologic, radiographic, and clinical correlation. She was found to have a clival mass extending into the sphenoid sinus. Surgical excision was performed by both the otolaryngology and neurosurgery departments at a single institution. She underwent an extended endoscopic endonasal resection of the clival mass. Following surgery, the numbness on the left V2 and V3 distribution improved. She occasionally reported bilateral V3 distribution symptoms without definite anatomic correlates for right sided complaints. Due to the presence of residual tumor, we recommended adjunctive medical therapy. We performed adjunctive medical therapy with Denosumab, a RANKL inhibitor. Discussion When complete surgical excision with negative margins is not feasible in lesions of the skull base, adjuvant treatment is commonly required to achieve local disease control. Our case demonstrates the efficacy of a combined approach where surgery is used to achieve a histologic diagnosis, decompression and evaluate for respectability. Adjuvant medical therapy using RANKL inhibitors is a promising approach that may be effective to achieve lifelong disease control but requires continued maintenance on therapy. Citation Format: Myra A. Zaheer, Abhisri Ramesh, Aadit P. Mehta, Adriana S. Fonseca, Daniel A. Donoho. Short-term outcomes of an extended endoscopic endonasal resection of a clival giant cell tumor with adjuvant RANK-L inhibitor therapy: Case report [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Innovating through Basic, Clinical, and Translational Research; 2023 Jul 7-8; Montreal, QC, Canada. Philadelphia (PA): AACR; Clin Cancer Res 2023;29(18_Suppl):Abstract nr PO-099.

JS06.5.A TUCATINIB, TRASTUZUMAB, AND CAPECITABINE WITH STEREOTACTIC RADIOSURGERY IN PATIENTS WITH BRAIN METASTASES FROM HER-2 POSITIVE BREAST CANCER (TUTOR): A MULTICENTER PHASE 1 CLINICAL TRIAL

Abstract BACKGROUND 20-40% of HER-2-positive breast cancer patients develop brain metastases (BMs), for which stereotactic radiosurgery (SRS) is used for local disease control. Tucatinib, an oral HER-2-selective tyrosine kinase inhibitor (TKI), has been demonstrated to be safe and efficacious in HER-2-positive breast cancer in combination with capecitabine and trastuzumab. The synergism between these three drugs and radiation may potentially enhance DNA damage, causing increased apoptosis. We hypothesize that this 3-drug therapy, in combination with SRS in patients with HER-2 positive breast cancer BM (BCBM), may be safe and provide superior long-term control of intracranial and systemic disease. METHODS This is a prospective, single-arm, multicenter, ongoing, phase 1 clinical trial that aims to determine the safety of the combination therapy in patients with HER-2 positive BCBM. Patients aged 18-80 years, ECOG score 0-2, normal organ function, and up to 10 newly-diagnosed BMs are being enrolled at six centers in the US. Any number of prior systemic therapies are allowed, except tucatinib and capecitabine. Key exclusion criteria include leptomeningeal metastases documented by MRI or CSF evaluation, evidence of intra-tumoral or peri-tumoral hemorrhage, and BMs within 5 mm of the optic chiasm/nerve. The primary study endpoint is maximum tolerated dose (MTD) of tucatinib with SRS. This de-escalation study starts tucatinib at a dose level of 300 mg twice daily (BID). Dose level -1 is 250 mg BID, and dose level -2 is 200 mg BID. Up to 40 patients will be enrolled in this study based on a 3 + 3 design. We plan to expand the cohort at MTD to total of 40 patients to assess the safety and efficacy of drug combination. Secondary endpoints include efficacy as determined by response rate, intracranial progression-free survival (PFS), extracranial PFS, and overall survival. Neurocognitive outcomes are being assessed by Hopkins Verbal Learning Test, Controlled Oral Word Association, Trail Making Test Part A and B, and Grooved Pegboard Test. Acute and late toxicity is assessed using CTCAE v5.0. Quality of life is assessed by Functional Assessment of Cancer Therapy, including Brain Tumor module (FACT-Br). Patients are administered oral tucatinib with SRS as per the treating radiation oncologist, followed by oral tucatinib for two weeks which is the dose-limiting toxicity (DLT) period. This is followed by tucatinib, trastuzumab, and capecitabine until progression or intolerable toxicity. DLTs are defined by Grade 3 or 4 thrombocytopenia, grade 4 anemia, grade 4 neutropenia lasting more than seven days, febrile neutropenia, and any non-hematologic toxicity of grade 3 or greater (excluding alopecia). RESULTS Patient enrollment started in February 2023. CONCLUSION Findings from this trial will demonstrate the safety and efficacy of this combination treatment in BCBM (Clinical Trial Information: NCT05553522).

Metástasis vertebrales. Tratamiento en bloque

En bloc resection of vertebral metastases has been the subject of study in medical literature due to its impact on patients’ quality of life and effectiveness in local disease control. This bibliographic analysis examines the findings and perspectives of published studies concerning en bloc resection of oligometastases in the spine. The technique, which involves the complete removal of the tumour along with a portion of the surrounding bone, has been shown to improve local tumour control, reduce recurrence, and potentially prolong patient survival compared to conventional decompression and stabilization techniques. However, en bloc resection also presents risks and complications, such as surgical morbidity and extended recovery time. Appropriate patient selection, preoperative planning, and a multidisciplinary approach are essential to optimize outcomes. As new techniques and advances in adjuvant treatment develop, en bloc resection of oligometastases in the spine remains an area of interest in oncological research.

Relationship between transcriptional expression of pyruvate dehydrogenase and local control of disease in patients with oral cavity carcinomas

BackgroundThe altered cellular metabolism is one of the hallmarks of the cancer cells, favoring the process of aerobic glycolysis, known as the Warburg effect. The pyruvate dehydrogenase (PDH) complex is one of the elements involved in this metabolic process. The present study aims to evaluate the relationship between the transcriptional expression of PDHB and the risk of local recurrence in patients with oral cavity carcinomas. MethodsWe determined the transcriptional expression of PDHB in biopsies from 41 patients with oral cavity carcinomas treated with surgery. The PDHB expression was categorized according to the local control of the disease with a recursive partitioning analysis. ResultsDuring the follow-up period 13 patients (31.7%) had a local recurrence of the tumor. Considering local disease control as the dependent variable, the recursive partitioning analysis classified the patients in two categories according to high (n=16, 39.0%) or low (n=25, 61.0%) PDHB expression. Five-year local recurrence-free survival for patients with high PDHB expression was 84.8% (95% CI: 65.2-100%), and for patients with low expression it was 54.3% (95% CI: 34.3–74.2 %) (P=0.034). The results of multivariate analysis showed that patients with a low PDHB expression had a 4.90 times higher risk of local recurrence of the tumor (95% CI: 1.02–22.68, P=0.042). ConclusionThere is a relationship between the metabolic characteristics of the tumor and its aggressiveness. According to our results, patients with oral cavity carcinomas with low transcriptional expression levels of PDHB have a significantly higher risk of local tumor recurrence.

The outcome of early-stage glottic carcinoma patients treated with radiotherapy: Egyptian National Cancer Institute (NCI-Egypt) experience.

Radiotherapy (RT) is an appropriate treatment option for early-stage glottic cancer (ESGC) that achieves high local control and preserves voice quality. However, the optimal radiation treatment schedule remains unknown. We present our institution's 14-year experience in treating ESGC with definitive radiotherapy between 2005 and 2019 inclusively. We reviewed the medical records of 104 patients; 63 (60.5%) were treated with conventional fractionation (CF), and 41 (39.5%) were treated with hypofractionated radiotherapy (HF). The clinical T-stage was T1a in 50 patients (48%), T1b in 27 (26%), and T2 in 27 (26%). Age, gender, anterior commissure involvement, stage, radiotherapy technique, radiation fraction size, and overall treatment time (OTT) were analyzed as prognostic factors. The survival outcomes, local regional control (LRC), and laryngeal preservation rate were evaluated. The 5-year overall survival (OS) and LCR were 83.3% and 78%, respectively. On univariate analysis, treatment with CF (p = 0.02), prolonged OTT > 49 days in CF and > 40 days in HF (p = 0.04), and RT total dose < 66 Gy (p = 0.03) were associated with poor LRC. Multivariate analysis showed a non-significant association with LRC (all p > 0.05). The 5-year OS rate in the CF and HF-treated patients was 84.9% and 72.1%, respectively (p = 0.99), and in patients who had T1a, T1b, and T2 disease, were 78.2%, 96.0%, and 82.1%, respectively (p = 0.43). All patients and tumor variables showed no statistically significant association with OS. Only low-grade acute toxicity was observed. Non-inferiority results supported the HF schedule to ESGC, including high local disease control and decreased overall treatment time. Our study supports its efficacy in the primary care of ESGC with manageable side effects.

Definitive treatment for head and neck mucosal melanoma.

Head and neck mucosal melanoma is a rare clinical subtype of melanoma or head and neck cancer. Mucosal melanoma is aetiologically and molecularly distinct from cutaneous melanoma. The therapeutic efficacy of immune checkpoint inhibitors for head and neck mucosal melanoma remains unclear. Surgery is considered as the mainstay of treatment for locally advanced head and neck mucosal melanoma, and adjuvant radiotherapy has a role in local disease control. New treatment modalities, such as targeted therapy and immunotherapy, have changed the treatment of cutaneous melanoma. However, patients with mucosal melanoma have been excluded from most Phase III clinical trials. Due to its rarity, outcome data for locally advanced head and neck mucosal melanoma are scarce and are mainly based on retrospective studies with limited case numbers. The objective of this review was to provide an update and overview of clinical trials, prospective observational studies and retrospective studies and discuss future directions for multimodal treatment of locally advanced head and neck mucosal melanoma.

Should we exclude patients with peritoneal carcinosis of colorectal origin and high PCI from CRS + HIPEC?

International guidelines exclude from surgery patients with peritoneal carcinosis of colorectal origin and a peritoneal cancer index (PCI) ≥ 16. This study aims to analyze the outcomes of patients with colorectal peritoneal carcinosis and PCI greater or equal to 16 treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) (CRS + HIPEC). We retrospectively performed a multicenter observational study involving three Italian institutions, namely the IRCCS Policlinico San Matteo in Pavia, the M. Bufalini Hospital in Cesena, and theASST Papa Giovanni XXIII Hospital in Bergamo. The study included all patients undergoing CRS + HIPEC for peritoneal carcinosisfrom colorectal origin from November 2011 to June 2022. The study included 71 patients: 56 with PCI < 16 and 15 with PCI ≥ 16. Patients with higher PCI had longer operative times and a statistically significant higher rate of not complete cytoreduction, with a Completeness of Cytoreduction score (CC) 1 (microscopical disease) of 30.8% (p = 0.004). The 2-year OS was 81% for PCI < 16 and 37% for PCI ≥ 16 (p < 0.001). The 2-years DFS was 29% for PCI < 16 and 0% for PCI ≥ 16 (p < 0.001). The 2-year peritoneal DFS for patients with PCI < 16 was 48%, and for patients with PCI ≥ 16 was 57% (p = 0.783). CRS and HIPEC provide reasonable local disease control for patients with carcinosis of colorectal origin and PCI ≥ 16. Such results form the basis for new studies to reassess the exclusion of these patients, as set out in the current guidelines, from CRS and HIPEC. This therapy, combined with new therapeutical strategies, i.e., pressurized intraperitoneal aerosol chemotherapy (PIPAC), could offer reasonable local control of the disease, preventing local complications. As a result, it increases the patient's chances of receiving chemotherapy to improve the systemic control of the disease.

Analysis of the Peritumoral Tissue Unveils Cellular Changes Associated with a High Risk of Recurrence.

The management of soft-tissue sarcoma (STS) relies on a multidisciplinary approach involving specialized oncological surgery combined with other adjuvant therapies to achieve optimal local disease control. Purpose and Results: Genomic and transcriptomic pseudocapsules of 20 prospective sarcomas were analyzed and revealed to be correlated with a higher risk of recurrence after surgery. A peritumoral environment that has been remodeled and infiltrated by M2 macrophages, and is less expressive of healthy tissue, would pose a significant risk of relapse and require more aggressive treatment strategies.

Prevalence of antibodies to Toxocara canis and its associated risk factors in socio-economically deprived nomadic communities of Pakistan.

Toxocariasis is an important zoonotic disease caused by Toxocara (T.) canis with considerably higher prevalence in developing countries. The data on its epidemiology, especially in socioeconomically deprived nomadic communities, are scarce in Pakistan. Therefore, this study was conducted to determine the prevalence of anti-T. canis antibodies and its associated risk factors in nomadic communities located in and around Multan, Pakistan. A total of 184 sera samples were collected from nomadic communities by simple random sampling technique. The descriptive epidemiological data of participants were collected on well-designed questionnaires. Prior consent was also obtained from the participants to use the data generated from their samples without showing their identity. All the samples were analysed for the detection of anti-T. canis antibodies using commercially available Enzyme-Linked-Immunosorbent-Assay (ELISA) kits having 91% sensitivity and 96% specificity (Bordier Affinity Products, Switzerland). The overall seroprevalence of toxocariasis among nomadic communities was 27.7% (51/184). Various factors, including age, known disease history, nutritional status, contact with dogs, practice of hand washing after contact with dogs, use of unwashed vegetables, body mass index, and drug abuse, showed significant correlation (p < 0.05) with toxocariasis in nomadic communities. Conversely, other factors, including gender, marital status, educational status, awareness about zoonotic diseases, source of drinking water, occupation, location, hand washing before taking food, exposure to soil, and hygienic eating behaviour, showed non-significant correlation (p > 0.05) with seroprevalence of toxocariasis. Results also showed that >50% of seropositive cases were asymptomatic, whereas cough and abdominal pain were recorded in 19.6% and 11.76% of seropositive cases, respectively. Keeping in view, it is suggested to conduct surveys at mass level to rule out the exact disease status at national level and to include nomadic communities in local, national, and regional disease control programs through provision of better healthcare facilities and awareness about the disease.

Outcome of brain metastases from adrenocortical carcinoma: a pooled analysis

PurposeBrain metastases rarely complicate the natural history of patients with adrenocortical carcinoma (ACC). No information is available regarding the life expectancy and efficacy of treatments in ACC patients with brain involvement.MethodsA pooled analysis was performed by searching on PubMed and using the keywords: “brain metastases in adrenocortical carcinoma”, and “leptomeningeal metastases in adrenocortical carcinoma”. Four patients diagnosed at Spedali Civili Hospital in Brescia were added to the analysis. Data concerning demographic, disease characteristics, adopted treatments and patient prognosis were collected.ResultsA total of 27 patients (18 adults and 9 children) were included in this study, 22 of them had an adequate follow-up. Brain metastases occurred late in the natural history of adult patients but not in that of children. Surgery plus/minus radiation therapy was the treatment of choice. Adult patients with brain metastases had a poor prognosis with a median progression-free survival (PFS) and overall survival (OS) of 2 and 7 months, respectively. Median PFS and OS were not attained in children.ConclusionBrain metastases in ACC patients are rare and are associated with poor prognosis, particularly in adults. Surgery plus/minus radiotherapy is the only therapeutic approach that can offer patients a chance to obtain durable local disease control.

DIPG-52. EXTRAPONTINE PROGRESSION WITH STABLE PONTINE DISEASE POST-RADIOTHERAPY IN DIFFUSE INTRINSIC PONTINE GLIOMA (DIPG) ON A CONNECT TRIAL: IMPLICATIONS FOR RADIATION TREATMENT VOLUMES

Abstract Radiotherapy remains the only treatment modality proven to prolong survival and alleviate symptom burden for patients with DIPG. Upfront focal photon radiation to 54 Gy with 1-1.5cm margins is standard. Subventricular, leptomeningeal, and/or spinal dissemination is observed in up to 50% of cases at autopsy, with activation of metastasis-related pathways (eg, epithelial-mesenchymal transition) in a subset of tumors. Given potential for metastatic spread and critical implications for radiation field volumes, we analyzed the frequency of extrapontine disease progression with pontine tumor stability within a prospective cohort with standardized longitudinal imaging. In a CONNECT consortium-sponsored phase Ib trial with a radiosensitizing agent administered concurrently with focal radiation and adjuvantly, among 10 patients with DIPG who experienced progressive disease with available serial imaging, four (40%) had evidence of disease extension and/or non-contiguous dissemination with stable pontine tumor size at a median of 9 months (range: 5-15 months) from diagnosis. Specifically, extrapontine progression was observed in the spinal cord (n=3), cerebellum (n=2), basal ganglia (n=1), temporal lobe (n=1) and/or leptomeninges and ependymal surfaces (n=1), without radiographic pontine disease progression. Five of the remaining six patients (who came off treatment due to pontine progression) subsequently had radiographic evidence of extrapontine extension (cerebellar, spinal, thalamic, supratentorial). Comprehensive molecular profiling is underway on biopsy or autopsy specimens for three patients, focusing on metastasis pathways. In summary, within a small prospective cohort with longitudinal imaging, we observed extrapontine progression despite local pontine disease control following focal radiotherapy in 40% of patients with DIPG at a median of 9 months after diagnosis. Further research will be essential to identify biological predictors of dissemination and corroborate findings in a larger cohort, but results suggest at least a subset of patients with DIPG may benefit from larger radiation volume expansion into contiguous structures and white matter tracts.

Local disease control after stereotactic body radiotherapy in patients with neuroendocrine neoplasms: a cohort study

Background Neuroendocrine neoplasms represent a diverse group of malignancies. Anatomic origin, histology and aggressiveness vary extensively, from low-grade tumours with an indolent prognosis to highly aggressive conditions with poor outcome. Surgery, with a curative intent, is the standard of treatment when possible. Other treatment regimens include local treatment, or systemic therapy. The role of radiotherapy in treating neuroendocrine neoplasms is not yet established, but studies indicate that a high rate of local control can be achieved by high-dose radiotherapy. Stereotactic body radiotherapy (SBRT) is high dose of radiation delivered to a small volume. We aimed to investigate the one-year local control rate of SBRT in patients with neuroendocrine neoplasms. Material and Methods Patients with neuroendocrine neoplasms treated with SBRT between 2003 and 2021 were retrospectively identified. Patient characteristics and SBRT-details were collected by review of patient records and the radiotherapy planning charts. All types except for small cell lung cancer and brain metastases were allowed. The prescribed dose was 45–67.8 Gy in three fractions. Progression, both within the target-site and in other sites, was determined based on existing imaging reports. One-year local control rate and systemic control rate was calculated. Descriptive analyses of local response duration, progression-free survival and overall survival were performed. Results Twenty-one patients were included. The one-year local control rate was 94%. Four of the patients had local progression. All patients receiving SBRT towards their primary tumour (n = 11) had a bronchopulmonary neuroendocrine neoplasm, and a one-year local control rate of 100%. In patients treated at a metastatic target, 80% developed systemic progression but the local control remained high. Conclusion Our study suggests that SBRT may offer a feasible and effective treatment of neuroendocrine neoplasms in selected cases. SBRT provides long-term local stability and may be useful in treating patients with localised disease not fit for surgery.

Safety of Concurrent Radiation Therapy With Brentuximab Vedotin in the Treatment of Lymphoma

Purpose: Radiation therapy (RT) and the antibody-drug conjugate brentuximab vedotin (BV) are standard-of-care treatment options for patients with certain B and T-cell lymphomas; however, there are limited data exploring the safety of concurrent BV and RT (BVRT). We performed a single institutional retrospective review of 44 patients who received BVRT. Twenty percent of patients (9/44) developed new grade 2 or higher (G2+) hematologic toxicity (HT) after BVRT, which was associated with radiation dose (median dose of 35 Gy in those with new G2+ HT compared with 15 Gy in those without; P < .001). Acute G2+ elevation in aspartate transaminase or alanine transaminase level was associated with administration of concurrent chemotherapy with BVRT (57% vs 21%; P=.047) but was not associated with any RT factors. Local control (LC) was achieved in 24 of 42 patients (57%) with available follow-up. Ten patients (23%) proceeded to stem cell transplant or cellular therapy after BVRT at a median of 48 days (interquartile range, 27-188 days). At last follow-up, 10 patients (23%) remained without evidence of disease. Our analysis demonstrates that the combination of BV and RT is well tolerated, though care should be taken during RT planning to reduce the risk of HT. This combination can be considered for patients in need of both local and systemic disease control.