Real-word experience of pazopanib and sorafenib in patients with desmoid tumors: A CanSaRCC multi-center study.

BACKGROUND: Sorafenib and pazopanib, two tyrosine kinase inhibitors (TKI), are widely used in patients with progressive symptomatic desmoid tumors (DT). Limited real-word data is available on long-term outcomes of patients who progressed on, stopped, or continued TKIs. METHODS: Patients diagnosed with DTs and treated with sorafenib or pazopanib between 2011 and 2022 at 11 institutions were reviewed. Patient history, response to therapy and toxicity were recorded. Statistical analyses utilized Kaplan-Meier and log-rank tests. RESULTS: 142 patients with DT treated with sorafenib (n = 126, 88.7 %) or pazopanib (n = 16, 11.3 %) were analyzed. The median treatment duration was 10.8 months (range: 0.07- 73.9). The overall response rate and the disease control rate were 26.0 % and 95.1 %, respectively. The median tumor shrinkage was - 8.5 % (range -100.0 %- +72.5 %). Among responders, the median time to an objective response was 15.2 months (range: 1.1 to 33.1). The 1-year and 2-year progression-free survival rates were 82 % and 80 %. Dose reductions were necessary in 34 (23.9 %) patients. Grade 3 or higher adverse events were reported in 36 (25.4 %) patients. On the last follow-up, 55 (38.7 %) patients continued treatment. Treatment discontinuation (n = 85, 59.9 %) was mainly for toxicity (n = 35, 45.9 %) or radiological or clinical progression (n = 30, 35.3 %). For the entire cohort, 36 (25.4 %) patients required subsequent treatment. In the 32 responders, only 1 (3.1 %) patient required a subsequent treatment. In patients who discontinued TKI, 25 (44.6 %) with stable disease received subsequent treatment compared to 0 (0.0 %) of responders. CONCLUSION: This retrospective study represents the largest cohort of DT patients treated with sorafenib or pazopanib to date. Discontinuation of treatment in responders is safe. The optimal treatment duration in patients with stable disease remains to be defined.

Neoadjuvant Intra-arterial Cytoreductive Chemotherapy Improves Outcomes in Lacrimal Gland Adenoid Cystic Carcinoma.

BACKGROUND: Lacrimal gland adenoid cystic carcinoma (LGACC) has historically been associated with a poor prognosis even with localized disease, with a survival of 56% at 5 years. In 1988, we treated the first patient with neoadjuvant intra-arterial cytoreductive chemotherapy (IACC). Since then, we have used this protocol as the standard approach. We aim to analyze the outcomes of patients with LGACC treated with the protocol and compare them to a population-based cohort to assess if IACC can improve survival. METHODS: We prospectively assessed all non-metastatic patients with LGACC treated with IACC at a single institution between 1988 and 2021. For a comparison group, we identified all non-metastatic patients with LGACC treated with excision from the Surveillance, Epidemiology, and End Results (SEER) registry. We calculated disease-specific survival using the Kaplan-Meier and Cox proportional-hazards modeling methods. RESULTS: Thirty-five non-metastatic patients with LGACC treated with IACC were identified at a single institution, and 64 patients with non-metastatic LGACC treated with excision were identified in the SEER database. The 5- and 10-year disease-specific survival rates for patients treated with IACC were 84% (95%CI 71-97) and 76% (95%CI 60-92), respectively. While the 5- and 10-year disease-specific survival rates for the population-based cohort were 72% (95%CI 62-82) and 46% (95%CI 32-60). The survival analysis favored IACC, with a 60% lower risk of death (HR: 0.4; 95%CI 0.2-0.9). CONCLUSION: IACC improves disease-specific survival in comparison to a population-based cohort treated with excision. Additional patients treated with IACC at multiple institutions are required to provide further external validity.

Time to Cancer Treatment and Chemotherapy Relative Dose Intensity for Patients With Breast Cancer Living With HIV.

Importance: Patients with breast cancer and comorbid HIV experience higher mortality than other patients with breast cancer. Objective: To compare time to cancer treatment initiation and relative dose intensity (RDI) of neoadjuvant and adjuvant chemotherapy among patients with breast cancer with vs without HIV. Design, Setting, and Participants: A retrospective, matched cohort study enrolled women who received a diagnosis of breast cancer from January 1, 2000, through December 31, 2018. The electronic medical records of 3 urban, academic cancer centers were searched for women with confirmed HIV infection prior to or simultaneous with diagnosis of stage I to III breast cancer. Tumor registry data were used to identify 2 control patients with breast cancer without HIV for each participant with HIV, matching for study site, stage, and year of cancer diagnosis. Statistical analysis was performed from December 2022 to October 2023. Exposure: HIV infection detected before or within 90 days of participants' breast cancer diagnosis. Main Outcomes and Measures: The primary outcome was time to breast cancer treatment initiation, defined as the number of days between cancer diagnosis and first treatment. The secondary outcome was overall RDI for patients who received chemotherapy. These outcomes were compared by HIV status using Cox proportional hazards regression and linear regression modeling, respectively, adjusting for confounding demographic and clinical factors. Exploratory outcomes included instances of anemia, neutropenia, thrombocytopenia, and liver function test result abnormalities during chemotherapy, which were compared using Fisher exact tests. Results: The study enrolled 66 women with comorbid breast cancer and HIV (median age, 51.1 years [IQR, 45.7-58.2 years]) and 132 with breast cancer alone (median age, 53.9 years [IQR, 47.0-62.5 years]). The median time to first cancer treatment was not significantly higher among patients with HIV than those without (48.5 days [IQR, 32.0-67.0 days] vs 42.5 days [IQR, 25.0-59.0 days]; adjusted hazard ratio, 0.78, 95% CI, 0.55-1.12). Among the 36 women with HIV and 62 women without HIV who received chemotherapy, the median overall RDI was lower for those with HIV vs without HIV (0.87 [IQR, 0.74-0.97] vs 0.96 [IQR, 0.88-1.00]; adjusted P = .01). Grade 3 or higher neutropenia during chemotherapy occurred among more women with HIV than those without HIV (13 of 36 [36.1%] vs 5 of 58 [8.6%]). Conclusions and Relevance: This matched cohort study suggests that patients with breast cancer and HIV may have experienced reduced adjuvant chemotherapy RDI, reflecting greater dose reductions, delays, or discontinuation. Strategies for supporting this vulnerable population during chemotherapy treatment are necessary.

MRI T2 mapping assessment of T2 relaxation time in desmoid tumors as a quantitative imaging biomarker of tumor response: preliminary results.

Objectives: Because size-based imaging criteria poorly capture biologic response in desmoid-type fibromatosis (DF), changes in MRI T2 signal intensity are frequently used as a response surrogate, but remain qualitative. We hypothesized that absolute quantification of DF T2 relaxation time derived from parametric T2 maps would be a feasible and effective imaging biomarker of disease activity. Methods: This IRB-approved retrospective study included 11 patients with DF, managed by observation or systemic therapy, assessed by 3T MRI. Tumor maximum diameter, volume, and T2-weighted signal intensity were derived from manual tumor segmentations. Tumor:muscle T2 signal ratios were recorded. Two readers measured tumor T2 relaxation times using a commercial T2 scanning sequence, manual ROI delineation and commercial calculation software enabling estimation of reader reliability. Objective response rates based on RECIST1.1 and best responses were compared between size-based and signal-based parameters. Results: Median patient age was 52.6 years; 8 subjects were female (73%). Nine patients with longitudinal assessments were followed for an average of 314 days. Median baseline tumor diameter was 7.2 cm (range 4.4 - 18.2 cm). Median baseline T2 was 65.1 ms (range 40.4 - 94.8 ms, n=11); median at last follow-up was 44.3 ms (-32% from baseline; range 29.3 - 94.7 ms, n=9). T2 relaxation times correlated with tumor:muscle T2 signal ratios, Spearman p=0.78 (p<0.001). T2 mapping showed high inter-reader reliability, ICC=0.84. The best response as a percentage change in T2 values was statistically significant (mean -17.9%, p=0.05, paired t-test) while change in diameter was not (mean -8.9%, p=0.12). Conclusions: Analysis of T2 relaxation time maps of DF may offer a feasible quantitative biomarker for assessing the extent of response to treatment. This approach may have high inter-reader reliability.

Genomic Landscape of Angiosarcoma: A Targeted and Immunotherapy Biomarker Analysis.

We performed a retrospective analysis of angiosarcoma (AS) genomic biomarkers and their associations with the site of origin in a cohort of 143 cases. Primary sites were head and neck (31%), breast (22%), extremity (11%), viscera (20%), skin at other locations (8%), and unknown (9%). All cases had Next Generation Sequencing (NGS) data with a 592 gene panel, and 53 cases had Whole Exome Sequencing (WES) data, which we used to study the microenvironment phenotype. The immunotherapy (IO) response biomarkers Tumor Mutation Burden (TMB), Microsatellite Instability (MSI), and PD-L1 status were the most frequently encountered alteration, present in 36.4% of the cohort and 65% of head and neck AS (H/N-AS) (p < 0.0001). In H/N-AS, TMB-High was seen in 63.4% of cases (p < 0.0001) and PDL-1 positivity in 33% of cases. The most common genetic alterations were TP53 (29%), MYC amplification (23%), ARID1A (17%), POT1 (16%), and ATRX (13%). H/N-AS cases had predominantly mutations in TP53 (50.0%, p = 0.0004), POT1 (40.5%, p < 0.0001), and ARID1A (33.3%, p = 0.5875). In breast AS, leading alterations were MYC amplification (63.3%, p < 0.0001), HRAS (16.1%, p = 0.0377), and PIK3CA (16.1%, p = 0.2352). At other sites, conclusions are difficult to generate due to the small number of cases. A microenvironment with a high immune signature, previously associated with IO response, was evenly distributed in 13% of the cases at different primary sites. Our findings can facilitate the design and optimization of therapeutic strategies for AS.

A nonrandom association of breast implants and the formation of desmoid tumors.

BACKGROUND: Studies suggest that surgical breast augmentation with implants is a risk factor for breast desmoid tumors. The statistical strength of this correlation is unknown, as evidence is limited to anecdotal reports. METHODS: Patients with breast desmoid tumors and a history of breast implants seen at a single center between 2000 and 2021 were identified via radiology, breast, and sarcoma databases. The standardized incidence ratio (SIR) was calculated to assess the correlation between breast desmoid tumors and breast implants. The cases were pooled with published cases for analyses. Progression-free survival curves and hazard ratios were estimated using the Kaplan-Meier method and Cox proportional-hazards modeling. RESULTS: Fourteen patients from one institution and 66 cases in the literature were identified. All patients were female, and the mean age was 38 years old (range 20-66). 63 patients (82%) underwent resection, 9 (12%) received chemotherapy, 3 (4%) received sorafenib, 11 (14%) received hormonal therapy, and 3 (4%) underwent active surveillance. After resection, the 2-year recurrence-free survival rate was 77% (95% CI 65%-89%). The recurrence risk was lower for resection with no residual tumor (R0) compared to microscopic (R1) or macroscopic (R2) residual tumor (HR: 0.15; 95% CI 0.02-0.8; p < 0.05). The SIR was 482 (95% CI 259-775) to 823 (95% CI 442-1322), suggesting a 482-823 times higher risk of developing a breast desmoid tumor after breast augmentation than the general population. CONCLUSION: We present a nonrandom association between breast implants and desmoid tumors. Whether the tumors arise from the surgical trauma or the implant's biomaterial is unknown. When surgery is indicated, negative margins reduce the risk of recurrence.

Immunotherapy Strategies for Gastrointestinal Stromal Tumor.

Gastrointestinal stromal tumors (GIST) are the most common mesenchymal soft tissue sarcoma of the gastrointestinal tract. The management of locally advanced or metastatic unresectable GIST involves detecting KIT, PDGFR, or other molecular alterations targeted by imatinib and other tyrosine kinase inhibitors. The role of immunotherapy in soft tissue sarcomas is growing fast due to multiple clinical and pre-clinical studies with no current standard of care. The potential therapies include cytokine-based therapy, immune checkpoint inhibitors, anti-KIT monoclonal antibodies, bi-specific monoclonal antibodies, and cell-based therapies. Here we provide a comprehensive review of the immunotherapeutic strategies for GIST.

Prevalence of Targetable Mutations in Black Patients With Lung Cancer: A Systematic Review and Meta-Analysis.

PURPOSE: Inferior outcomes of Black patients with lung cancer compared with other racial groups are often linked to socioeconomic factors. It is crucial to determine whether a varying prevalence of targetable mutations limits treatments and contributes to disparities. MATERIALS AND METHODS: We conducted a meta-analysis on the prevalence of lung cancer EGFR, ALK, ROS-1, and BRAF mutations in Black patients compared with White, Hispanic, and Asian patients. We searched PubMed/MEDLINE, Cochrane Library, EMBASE, CENTRAL, Google Scholar, and clinicaltrials.gov databases. We selected studies reporting the prevalence of at least one mutation in the Black population. We calculated the pooled prevalence of mutations using fixed effects, exact binomial distributions, and Freeman-Turkey double arcsine transformation to stabilize the variances. RESULTS: Twenty studies with 11,867 patients were included. In Black patients, EGFR was the most prevalent mutation (6%; 95% CI, 5 to 7), followed by BRAF (1%; 95% CI, 0 to 2), ALK (1%; 95% CI, 0 to 2), and ROS-1 (0%; 95% CI, 0 to 1). Black patients had a lower prevalence of EGFR mutations than White, Hispanic, and Asian patients (P < .01). BRAF mutations were less prevalent in Black compared with White patients (P < .05), and ALK mutations were less prevalent when compared with Hispanic patients (P < .05). CONCLUSION: EGFR is the most frequent mutation found in Black patients, although its prevalence is lower than that in other races. Black patients have a low overall prevalence of ALK, ROS-1, and BRAF mutations. Given that disproportional eligibility for targeted therapies may be contributing to inferior outcomes, research focused on the Black population is needed to evaluate specific tumor characteristics and therapeutic strategies.

Acute generalised exanthematous pustulosis associated with shock.

A 23-year-old man with a history of end-stage renal disease was admitted to the hospital due to fever and shock, which occurred during his dialysis. One week prior, he developed an erythematous rash on his chest, face and back, associated with generalised eruption of pustules. In hospital, his status did not improve with norepinephrine and empirical broad-spectrum antibiotics. Following this, methylprednisolone was administered with remarkable improvement. Cultures revealed no infectious aetiology. Based on the morphology of the rash and a compatible skin biopsy, the diagnosis of acute generalised exanthematous pustulosis (AGEP) was established and considered the cause of his shock. The causative agent of his AGEP remained unknown. AGEP is a rare condition, most frequently associated with drug exposure. The removal of the offending agent is the treatment of choice. It can be complicated by shock in rare cases. In that scenario, systemic corticosteroids seem to improve outcomes greatly.

High-grade B-cell lymphoma with MYC and BCL6 rearrangements presenting as a cervical mass.

Lymphoid malignancies represent 0. 008% of all cervical tumours. While uncommon, lymphoid malignancies of the gynaecological tract require careful diagnosis and classification to ensure appropriate treatment. We present a case of a 54-year-old woman with HIV who presented with urinary and faecal incontinence for 2 weeks, associated with the feeling of a mass in her vagina. A smooth flesh-coloured pelvic mass was seen on physical examination, and a transvaginal biopsy revealed infiltration of atypical lymphoid cells with fluorescence in situ hybridisation positive for MYC and BCL6, and negative for IGH/BCL2. Bone marrow and cerebral spinal fluid analysis also showed involvement by atypical lymphocytes. She was diagnosed with stage IV high-grade B-cells lymphoma (HGBLs) with MYC and BCL6 rearrangements. She was given R-CODOX-M plus IVAC with no evidence of disease at 4-month follow-up. To our knowledge, this is the first literature report of a HGBL with MYC and BCL6 rearrangement presenting as a cervical mass.

Giant bullous emphysema mistaken for traumatic pneumothorax.

INTRODUCTION: Giant bullous emphysema (GBE) is defined by giant bullae in one or both upper lobes, occupying at least one-third of the hemithorax and compressing the surrounding parenchyma [1]. Symptoms include dyspnea, hypoxia, chest pain and pressure, and hemoptysis [2], which can be complicated by pneumothorax and infection of the bullae [3]. CASE PRESENTATION: A 50-year-old male was brought to the emergency department after he fell 5 m in a suicide attempt. The patient was in respiratory distress and had bilateral absence of breath sounds. He was intubated and bilateral chest tubes were inserted. A computerized tomography (CT) scan showed bilateral giant bullous emphysema in the upper lobes, confirming a diagnosis of GBE. As a result of the insertion of chest tubes, he developed bilateral high flow fistulas. During his hospitalization, he developed sepsis secondary to ventilator-associated pneumonia. In an attempt to control the fistulas, a right bullectomy was performed. Despite antibiotic treatment and surgical intervention, the patient died due to septic shock. DISCUSSION: The clinical picture of a patient with GBE can be similar to that of pneumothorax, and GBE has been reported as being misdiagnosed as pneumothorax [4,5]. A CT scan can play an important role in differentiating these conditions [6], thus avoiding needle decompression, which can be catastrophic [6]. CONCLUSION: Giant bullous emphysema can represent a pitfall in trauma assessment. We recommend that in cases where pneumothorax is suspected, if the patient is clinically stable, imaging studies should be performed prior to chest tube placement.

Transhiatal esophagectomy with gastric pull-up, pyloric exclusion and Roux-en-Y gastroenterostomy for the management of esophageal caustic injury.

INTRODUCTION: Ingestion of caustic materials can lead to digestive tube perforation involving the mouth, pharynx, esophagus and stomach (Vezakis et al., 2016 [1]). In this case report, the authors opted for gastric pull-up in a case of esophageal and pyloric stenosis secondary to caustic ingestion, and a Roux-en-Y gastroenterostomy in the lower portion of the gastric pull-up. PRESENTATION OF CASE: A 37 years-old male presented complaints of dysphagia, which had started 28 days before admission after the ingestion of a caustic liquid. An esophagogastroduodenoscopy was performed, and showed a complete occlusion of the esophagus, without the possibility of performing an esophagus dilatation or placing a nasoenteric tube. The option was made for a transhiatal esophagectomy with gastric pull-up, pyloric exclusion and Roux-en-Y gastroenterostomy. The patient was later admitted with a stenosis of the esophageal anastomosis, which was resolved after performing endoscopic dilatation. DISCUSSION: The medical team opted to use the stomach for the reconstruction of the gastrointestinal transit due to less morbidity during manipulation of that organ, as well as safer anastomosis, when compared to the colon. In this case report, the esophagus and pylorus were generally compromised, however, with no apparent damage whatsoever in the stomach. Therefore, we opted to resect the esophagus and used the stomach to perform a gastric pull-up with the exclusion of the pylorus and reconstruction with a Roux-en-Y gastroenterostomy. CONCLUSION: The proposed surgery is an option when dealing with similar cases, where endoscopic dilatation is not an option, and there is an associated pyloric stenosis.

Localized pancreatic Castleman disease presenting with extrahepatic dilatation of bile ducts: A case report and review of published cases.

INTRODUCTION: Castleman disease (CD) is a rare polyclonal lymphoproliferative disorder of unknown etiology, which usually develops in the mediastinum. It can also occur in the cervical, retroperitoneal and axillary regions. Localized pancreatic CD is quite rare [1]. PRESENTATION OF CASE: The authors herein present a case of a 34 years old female that was diagnosed during a symptomatic cholelithiasis evaluation. During the evaluation, an abdominal ultrasonography revealed a tumor at the head of the pancreas, which went on to generate a dilatation of the extrahepatic bile ducts. This finding was confirmed by abdominal magnetic resonance imaging (MRI). Subsequently, the patient underwent a laparotomy, where a capsulated tumor was found at the head of the pancreas with well-defined margins. The decision was made for tumor excision. The histopathology and immunohistochemistry established CD, hyaline vascular variation. DISCUSSION: The authors of the present paper also performed a literature review concerning Pancreatic CD, where there were found only 33 cases until the time of the writing of this paper, and we have subsequently carried out a retrospective analysis of all cases. In a patient with atypical images, there might be a benefit from a preoperative diagnosis of CD, by using immunohistochemistry analysis in an image guided biopsy. Thus, avoiding unnecessary procedures and surgeries. CONCLUSION: Localized pancreatic CD is a very rare condition with good prognosis, but it can mimic many common diseases, such as gastrointestinal stromal tumor (GIST), pancreatic neuroendocrine tumor or pancreatic adenocarcinoma.

Tumor Desmoplásico de Pequenas Células Redondas: Relato de caso / Desmoplastic Small-Round-Cell Tumor: Case Report / Tumor Desmoplásico de Células Pequeñas y Redondas: Relato de Caso

Introdução: O tumor desmoplásico de pequenas células redondas é uma rara neoplasia que se inicia e se espalha pela superfície peritoneal. Foi descrito pela primeira vez em 1989 e, em 1991, houve seu reconhecimento como entidade clínica e patológica distintas. Relato do caso: Homem de 34 anos apresentou quadro de dor abdominal e perda de peso, evoluindo para obstrução intestinal dois meses após. A laparotomia demonstrou grande massa abdominopélvica irressecável. O laudo anatomopatológico associado à imuno-histoquímica evidenciou diagnóstico de tumor desmoplásico de pequenas células redondas. A tomografia computadorizada confirmou derrame pleural bilateral, implantes peritoneais e massas abdominais e pélvicas. Realizou-se quimioterapia com carbo/taxol com intervalo de 21 dias. Substituiu-se o esquema para VAC/IE com intervalo de 21 dias, com resposta parcial, porém ainda se mantendo um tumor irressecável. Houve piora progressiva da performance do paciente, com evolução ao óbito por obstrução intestinal no 15º mês de seguimento. Conclusão: O tumor desmoplásico de pequenas células redondas, em razão da sua raridade, continua sendo um desafio para o diagnóstico e o tratamento.

Introduction: The desmoplastic small round cell tumor is a rare neoplasm that starts and spreads through the peritoneal surface. It was first described in 1989 and in 1991 was recognized as a distinct clinical and pathological entity. Case report: A 34-year-old man presented with abdominal pain and weight loss, progressing to an intestinal obstruction after two months. Laparotomy showed an unresectable abdominopelvic mass. Anatomopathological an immunohistochemistry analysis showed a desmoplastic small-round-cell tumor. Computerized Tomography showed bilateral pleural effusion, peritoneal implants, along with masses in the abdominal and pelvic region. Chemotherapy with carbo/taxol was administered at intervals of 21-days. Later, the chemotherapy was changed to VAC/IE at a 21-day interval, with a partial response, but it was still an unresectable tumor. There was a worsening in patient performance, and he died of an abdominal obstruction on the 15º month of follow-up. Conclusion: Due to its rarity, the desmoplastic small-round-cell tumor, is still a diagnostic and treatment challenge.

Introducción: El tumor desmoplásico de células pequeñas y redondas es una neoplasia rara que comienza y se disemina a través de la superficie peritoneal. Fue descrito por primera vez en 1989 y en 1991 fue reconocido como una entidad clínica y patológica distintas. Relato del caso: Un hombre de 34 años presentó dolor abdominal y pérdida de peso, progresando a una obstrucción intestinal después de dos meses. La laparotomía mostró una masa abdominopélvica irresecable. El análisis anatomopatológico e inmunohistoquímico mostró un tumor desmoplásico de células pequeñas y redondas. La tomografía computarizada mostró derrame pleural bilateral, implantes peritoneales y masas en la región abdominal y pélvica. Se administró quimioterapia con carbo/taxol en un intervalo de 21 días. Más tarde, la quimioterapia cambió a VAC/IE con un intervalo de 21 días, con una respuesta parcial, pero seguía siendo un tumor irresecable. Hubo un empeoramiento en el estado del paciente, y murió de una obstrucción intestinal en el 15º mes de seguimiento. Conclusión: Debido a su rareza, tumor desmoplásico de células pequeñas y redondas, sigue siendo un desafío de diagnóstico y tratamiento.