Visceral Involvement Research Articles

A-151 Secondary Malignancy and Visceral Involvement in Cutaneous T-Cell Lymphoma: Diagnostic Differentiation

A-151 Secondary Malignancy and Visceral Involvement in Cutaneous T-Cell Lymphoma: Diagnostic Differentiation

CASE REPORT ON DRESS SYNDROME INDUCED BY ANTITUBERCULOSIS DRUGS

Drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe adverse drug reaction characterized by an extensive skin rash in association with visceral organ involvement, lymphadenopathy, eosinophilia, and atypical lymphocytosis. We report a rare case of DRESS Syndrome secondary to anti tubercular treatment (ATT). A 53 year old male with pulmonary tuberculosis (TB) presented with fever, facial puffiness, bilateral pedal edema, itchy exfoliative rashes over face, thorax, abdomen, and extremities for 15 days after about 4 months of starting FDC of ATT. On examination there was hypotension (BP-80/60 mm Hg) and bilateral diffuse symmetrical exfoliative dermatitis over face, chest, abdomen, all 4 extremities sparing flexor aspect of thighs and legs. Investigations revealed eosinophilia, leucocytosis (predominantly lymphocytosis), raised alkaline phosphatase and acute kidney injury. FDC was withheld, skin biopsy was performed and the patient was managed as DRESS syndrome fulfilling diagnostic criteria with oral steroids (prednisolone 1mg/kg/day) and other supportive medications. The patient improved gradually with improvement in most of the symptoms and progressive return of laboratory parameters towards normal level. Individuals diagnosed with pulmonary TB who are undergoing treatment with FDC of ATT have a heightened susceptibility to DRESS. The timely identification and cessation of the offending agent can effectively mitigate mortality.

Safety and Efficacy of Extracorporeal Photopheresis for Acute and Chronic Graft-versus-Host Disease.

Background/Objectives: Despite novel biological agents, steroid-dependent or -refractory graft-versus-host disease (GvHD) remains a severe complication of allogeneic hematopoietic cell transplantation (allo-HCT). Extracorporeal photopheresis (ECP) is an alternative, non-immunosuppressive treatment for patients with acute (aGvHD) or chronic (cGvHD) GvHD. The aim of this study was to investigate the safety and efficacy of ECP in the treatment of acute and chronic GvHD; Methods: We prospectively studied 112 patients with cGvHD who received one or more previous lines of treatment and 28 patients with steroid-dependent or refractory grade II-IV aGvHD post-alloHSCT. Results: In terms of severe aGvHD, most of the patients (19/28) responded to ECP treatment, while the five-year overall survival (OS) was 34%. After adjustment for several confounder factors, the reduction in immunosuppression (p = 0.026) and number of ECP sessions (p < 0.001) were associated with improved OS. Regarding chronic GvHD, only 19 patients failed to respond to ECP treatment; though significantly lower rates of response were presented in patients with visceral involvement (p = 0.037) and earlier post-transplant GVHD diagnosis (p = 0.001). Over a follow-up period of 45.2 [interquartile range (IQR): 5.6-345.1] months, the 5-year cumulative incidence (CI) of cGvHD-related mortality was 21.2% and was significantly reduced in patients with ECP response (p < 0.001), while the 5-year OS was 65.3%. Conclusions: Our results confirm the safety and efficacy of ECP in patients with GvHD and provide sufficient data for further investigation and the best combination drugs needed such that GvHD will not be the major barrier of allo-HCT in the near future.

Donor-derived bartonellosis in solid organ transplant recipients from unhoused donors in Alberta

Bartonella quintana infection is rarely described to be transmitted through solid organ transplant (SOT). We report a cluster of using donor-derived B quintana infection and the attack rate from Bartonella seropositive donors. In this retrospective study of SOT recipients that received an organ from an unhoused deceased donor (UDD) in Alberta in 2022-2023, serology testing for Bartonella was performed indirect immunofluorescent assay on UDDs and recipients of UDDs with positive serology. Titers ≥1:64 were considered positive. During the study period, 31/32 UDDs were tested for immunoglobulin G to Bartonella (20 negative, 11 positive for B quintana and/or B henselae). Thirty-two organs were transplanted from the 11 seropositive donors. Six SOT recipients developed bartonellosis secondary to B quintana (4 SOT recipients received organs from 3 seropositive donors, and 2 SOT recipients from 1 UDD with no stored sample for testing). The attack rate for clinical disease from positive donors was 12.5% (4/32). The main presentation was skin nodules/papules (median 5.5 months) with bacillary angiomatosis in 4/6. Bartonella serology was positive in 5/6 SOT recipients (initially negative in 2) and blood B quintana quantitative polymerase chain reaction in 1. None had visceral involvement. All donors had history of substance use. This outbreak of bartonellosis reinforces the potential for unexpected donor-transmitted infections. Clinicians should be aware of high transmission of B quintana through transplant from infected UDDs.

VL-HIV co-infection with Leishmania containing skin lesions resembling para-kala-azar dermal leishmaniasis.

Leishmaniases are a group of neglected vector-borne infectious diseases that are among the six priority endemic diseases worldwide. Visceral leishmaniasis (VL) is the most severe clinical manifestation, characterized by systemic and chronic visceral involvement and high mortality in immunosuppressed and untreated patients. VL can be complicated into post-kala-azar dermal leishmaniasis (PKDL), and when dermatologic disorders occur simultaneously with active VL, an intermediate clinical form called para-kala-azar dermal leishmaniasis (para-KDL) occurs. This clinical form is of great epidemiological relevance, as humans act as a source of infection for vectorial transmission. In the Americas, Brazil is among the seven countries responsible for more than 90% of VL cases, though reports of PKDL and para-KDL are rare. This paper presents three cases of VL-HIV co-infection with Leishmania-containing skin lesions resembling para-kala-azar dermal leishmaniasis. The cases were investigated by the team from the Infectious Diseases Department of University Hospital (HUMAP/UFMS) in Mato Grosso do Sul, Brazil. The three patients exhibited skin lesions where amastigote forms of L. (L.) infantum were identified. All cases exhibited similar clinical manifestations of para-KDL, including fever, hepatosplenomegaly, pancytopenia, and disseminated skin lesions. The study described the prevalence of comorbidities, the incidence of VL relapse, and the therapeutic regimen in relation to the outcomes. The study underscores the importance of follow-up and secondary prophylaxis in patients with VL, which are essential for the efficacy of the treatment. Furthermore, the study provides insight into the potential epidemiological profile of para-KDL cases in Brazil, which contributes to the development of more efficient clinical management strategies for patients.

Clinicopathologic Correlation and Routine Immunostains Help Distinguish Congenital Disseminated Pyogenic Granuloma From Other Cutaneous Disseminated Vascular Proliferations of Infancy: Case Report and Literature Review.

The presence of multiple cutaneous vascular lesions in infancy can signal the possibility of visceral involvement. Dermatopathologists must appreciate how the differential diagnosis includes entities that have distinct therapeutic and prognostic implications. Fortunately, these rare entities can be distinguished histopathologically with the help of clinicopathologic correlation and immunohistochemistry. In this article, we discuss congenital disseminated pyogenic granuloma, multifocal infantile hemangioma, and multifocal lymphangioendotheliomatosis with thrombocytopenia. Subtle morphologic and immunophenotypic features permit their distinction, which in turn is important for identifying extracutaneous manifestations and effective treatments. We present a case of a 3-week-old infant with congenital disseminated pyogenic granuloma involving the skin and the liver whose lesions regressed without therapeutic intervention over 6 months of close follow-up. We review the literature on these rare, overlapping entities and present an approach to resolving the differential diagnosis.

Investigating Combination Therapy: The Role of Lutetium-177 PSMA-617 Radioligand Therapy and Androgen Receptor Pathway Inhibitors in Metastatic Castration-Resistant Prostate Cancer.

Background: The combination of Lutetium-177 (Lu-177) PSMA-617 radioligand therapy (RLT) with androgen receptor pathway inhibitors (ARPIs) has shown promise in metastatic castration-resistant prostate cancer (mCRPC). However, real-world data on the efficacy and safety of this combination are limited. This study aimed to evaluate the impact of combination therapy with Lu-177 PSMA-617 RLT and ARPIs on progression-free survival (PFS) and overall survival (OS) in patients with mCRPC. Methods: In this retrospective study, 104 mCRPC patients receiving Lu-177 PSMA-617 RLT at our institution between December 2017 and January 2024 were divided into the following two groups those receiving Lu-177 PSMA-617 RLT plus ARPI (n = 34) and those receiving Lu-177 PSMA-617 RLT alone (n = 70). Patients received 150 to 200 millicuries Lu-177 PSMA-617 RLT in each cycle. PFS and zOS were assessed using Kaplan-Meier analysis and Cox proportional hazard models. Results: The combination therapy significantly prolonged median PFS compared to Lu-177 PSMA-617 RLT alone (11 vs. 5.6 months; HR, 0.47; 95% CI, 0.28-0.79; p < 0.01). A trend towards improved OS was also observed in the combination group (20.3 vs. 15.9 months; HR, 0.58; 95% CI, 0.33-1.02; p = 0.06). Age was a significant predictor of OS (21.2 vs. 12.4 months for younger vs. older patients; p < 0.01), while Gleason score and visceral involvement did not significantly impact PFS. The safety profile indicated that adverse effects were generally comparable between the two groups, with no statistically significant differences in the incidence of anemia, neutropenia, thrombocytopenia, nephrotoxicity, or hepatotoxicity. Conclusions: This study provides evidence that combining Lu-177 PSMA-617 RLT with ARPIs may significantly improve PFS in mCRPC patients. The potential OS benefit warrants further investigation in larger prospective trials. Age should be considered when making treatment decisions for mCRPC patients.

Imaging in Abdominal Tuberculosis

AbstractDiagnosis of abdominal tuberculosis is challenging due to its variable imaging appearance, which can mimic several other conditions. This review covers the imaging spectrum of tubercular involvement of abdominal lymph nodes, peritoneum, solid abdominal viscera, and the gastrointestinal tract. Tubercular lymphadenitis is the most frequent manifestation of abdominal tuberculosis and may show necrosis. Peritoneal tuberculosis is the next most commonly involved site in the abdomen and can be of wet, fibrotic, and dry forms. The ileocecal region is the most common site of involvement in gastrointestinal tuberculosis. Solid visceral involvement mostly affects the liver and spleen causing hepatosplenomegaly with a micronodular or macronodular imaging pattern. Awareness of the spectrum of imaging manifestations and a high index of suspicion is required to reach the correct diagnosis.

Evisceration due to full thickness injury to the abdominal wall, with intestinal involvement, plus trauma to the chest wall, extremities and genitals due to high voltage electrical burn; case report and review of the literature

Electrical burns are one of the most drastic traumas to which an individual can be exposed; being able to directly or indirectly compromise almost all tissues of the human body. They cause more than 3,000 admissions to specialized burn units in the United States. Up to 40% of serious electrical injuries are fatal, resulting in approximately 1000 deaths per year.Its incidence depends on the type of exposure to electricity: low voltage, due to contact with electrical cables or plugs. High voltage, due to occupational exposures and power lines while climbing trees or poles. These voltages are more likely to cause injuries to deep tissues and internal organs compared to low voltage injuries and also the degree of body surface area burned.Its approach constitutes a challenge, since the risks of visceral involvement are added to the morbidity and mortality inherent to the burn. Early treatment of intra-abdominal complications allows a more conservative approach, reducing ostomies and their associated comorbidity. It is preferable to manage the abdominal defect by preserving the tissues themselves and restoring the midline. In our case, it was feasible to perform a primary closure of the abdominal wall. Your treatment will depend on factors such as: the amount of tissue lost, intra-abdominal contamination, general condition, and factors such as: physical resources and experience of the hospital. Mortality from burns ranges between 3 and 55%, those with the highest risk of death are those at extreme ages, higher degrees of burns, injuries associated with inhalation, and injuries in patients with comorbidities.

Acute ulcerated botryomycosis in an immunocompromised patient

Botryomycosis is a rare chronic granulomatous bacterial infection with approx. 200 reported cases worldwide. The most common microorganism associated with this condition is Staphylococcus aureus. Botryomycosis manifests itself across a spectrum of lesions with a characteristic histological feature known as the Splendore–Hoeppli phenomenon. Herein, we report the case of a 35-year-old female presenting with an ulcerated lesion and a previous diagnosis of lymphoblastic leukemia. Botryomycosis should be considered in immunosuppressed patients with ulcerated lesions. Treatment duration may range from four to eight weeks, with debridement if necessary. It is essential to exclude visceral involvement. Key words: Botryomycosis, Staphylococcus aureus, Lymphoblastic leukemia, Immunosuppression

Real-world Outcomes of Dual HER2 Blockade Therapy in Metastatic HER2-Positive Breast Cancer: from Induction to Maintenance.

Dual human epidermal growth factor receptor 2 (HER2) blockade with trastuzumab and pertuzumab combined with taxane-based chemotherapy (Cht) has been the standard first-line treatment for HER2-positive metastatic breast cancer (mBC) for years, due to the impressive results of the CLEOPATRA study. Real-world (RW) studies have become critical for assessing treatment effectiveness and safety in real-life circumstances. The aim of this study was to analyze the treatment outcomes of first-line therapy for HER2-positive mBC in RW clinical practice, specifically focusing on the use of maintenance endocrine therapy (ET) in hormone receptor positive (HR-positive) patients. This retrospective analysis included 106 HER2-positive mBC patients treated with trastuzumab and pertuzumab combined with taxane-based Cht from October 2015 to December 2020 at the University Hospital Centre Zagreb. At a median follow-up of 30 months, median progression-free survival (PFS) was 25 months for the total population (95% confidence interval [CI] 16- not analyzed). Patients with de novo mBC had longer median PFS than patients with recurrent disease (not reached vs. 18 months; hazard ratio 1.99; 95% CI 0.69-3.64, p<0.022). Age, hormone receptor positivity, visceral involvement, number of Cht cycles and previous adjuvant trastuzumab did not impact PFS. Most HR-positive patients (N=55, 88.7%) received maintenance ET after induction Cht. This retrospective study provides additional data on patient characteristics, treatment and outcomes of RW HER2-positive mBC patients treated with pertuzumab and trastuzumab as first-line therapy. In our institution, maintenance ET after induction Cht has become standard clinical practice.

Isolated visceral manifestation of Buerger’s disease presenting as intestinal obstruction: a case report

Introduction and importance: Buerger’s disease is an uncommon segmental nonatherosclerotic vasculitis essentially affecting small to medium-sized arteries and veins of upper and lower extremities and can lead to limb amputation. Visceral vessel involvement is quite rare accounting for 2% of cases presenting with acute abdomen due to mesenteric ischemia. Moreover, isolated visceral involvement is even rare. Case presentation: A 42-year-old gentleman, a chronic smoker, presented with abdominal pain associated with nausea and vomiting and loose stool of 2 months duration. Magnetic resonance enterography revealed segmental circumferential wall thickening with stricture in the mid part of the jejunum with lymphadenopathy features of possible inflammatory bowel disease (Crohn’s disease). Furthermore, intraoperative surgical findings were also suggestive of Crohn’s disease. However, histologic findings were consistent with thromboangiitis obliterans. Discussion: Thromboangiitis obliterans can present with inflammatory vascular lesions without necrosis in the early stage to varying degrees of recanalisation, gangrene, and amputation in the late stage. It rarely involves the brain, heart, and abdominal viscera. The visceral involvement may be in the form of intestinal obstruction or mesenteric ischemia or can mimic Crohn’s in a background of smoking. Conclusion: This case report will help to learn more about the rarer intestinal presentation of intestinal Buerger’s disease. It can present with features of bowel ischemia, obstruction or Crohn’s. So, histology would play a pivotal role in differentiating the diagnostic dilemma.

Hemangiomatosis hepática de inicio neonatal

Infantile hemangioma is the most frequent pediatric benign tumor. The involvement is usually cutaneous, but it can be visceral too. Some presentations pose a diagnostic challenge and can even be life-threatening. We present two cases that consulted to our center. The first is a 13-day-old female newborn, who presents with an increase in the number and size of erythematous micromacules-papules, which she already had. She is diagnosed with infantile hemangiomatosis. In the extension study, the abdominal ultrasound shows multiple hepatic hemangiomas. The evolution is favorable without treatment, disappearing almost all hemangiomas within the first year. The second case is a 37-day-old infant, who presents with propulsive vomiting and abdominal distention. The physical exam is remarkable for cutaneous jaundice and 4cm hepatomegaly. Blood tests show cholestatic hepatitis without liver failure and hypothyroidism. Abdominal ultrasound shows diffuse hepatic hemangiomatosis, which is confirmed by MRI. Oral Propanolol and Levothyroxine are started. The evolution is favorable, with resolution of the hemangiomatosis. Hemangiomas are usually cutaneous but visceral involvement must be studied in the presence of more than 5 cutaneous hemangiomas or if they are large. Hepatic hemangiomas are the most common. They can be congenital (focal), which can involute spontaneously, or infantile (multifocal or diffuse), which can produce symptoms (cholestasis, hepatomegaly, heart failure, hypothyroidism…). The treatment is Propranolol and, in case of hypothyroidism, Levothyroxine. To conclude, we emphasize the importance of early diagnosis of hepatic hemangiomatosis because it has the possibility of specific and effective treatment.

Juvenile dermatomyositis with Anti-SAE antibodies in a Moroccan child associated with pseudo-angioedema: a case report

BackgroundJuvenile Dermatomyositis (JDM) is the leading cause of non-infectious inflammatory myopathy in children. It is a heterogeneous group of autoimmune diseases characterized by a variable combination of muscular, dermatological, and visceral involvement. Myositis-specific autoantibodies help define homogeneous subgroups with common clinical characteristics and prognoses. Anti-SAE (small ubiquitin-like modifier 1 (SUMO-1) activating enzyme) antibodies are among the most recently discovered specific autoantibodies. The presence of these antibodies is very rare, making it challenging to define clinical features and prognosis in the juvenile form. We report the first case of an African patient with juvenile dermatomyositis and positive anti-SAE antibodies.Case ReportA 5-year-3-month-old Moroccan boy presented to the pediatric emergency department with dysphagia that had been evolving for two days, preceded two months earlier by facial erythema associated with fatigue, lower limb pain, difficulty walking, and progressive inflammatory polyarthralgia. On admission, the child had a heliotrope rash with predominant pseudo-angioedema on the lips, periungual telangiectasia, and Gottron’s papules over the bilateral interphalangeal and metatarsophalangeal joints. The patient had a more pronounced proximal muscle weakness in the lower limbs. He had no urticaria, fever, arthritis, calcinosis, cutaneous ulcers, or lipodystrophy. The Joint examination was normal, as was the pleuropulmonary examination. The electroneuromyography showed myogenic changes in all four limbs. Laboratory findings showed elevated levels of creatine phosphokinase and lactate dehydrogenase and a mild inflammatory syndrome. The electrocardiogram was normal. The anti-SAE antibodies were positive. The boy was diagnosed with juvenile dermatomyositis. He received methylprednisolone bolus therapy followed by oral prednisone. The latter was gradually tapered in combination with weekly intramuscular methotrexate. As a result, dysphagia disappeared within 48 h. After two weeks, there was an improvement in the muscular score and a significant regression of facial pseudo-angioedema.ConclusionWe report the first African patient with anti-SAE autoantibody-positive JDM. He had a typical dermatological manifestation of JDM associated with pseudo-angioedema predominant on the lips; a rarely reported sign in DM and JDM patients. The patient responded well to corticosteroid therapy and methotrexate.

PARTIALLY REVERSIBLE DILATED CARDIOMYOPATHY ASSOCIATED WITH AMPHOTERICIN B THERAPY

Abstract Background Amphotericin B (AmB) is an antifungal drug commonly used in a broad spectrum of infections, including leishmaniasis. Leishmaniasis, transmitted through insect bites, has cutaneous, mucocutaneous, or visceral (particularly liver and spleen) involvement. The main adverse effects of AmB are cardiotoxicity and nephrotoxicity, often reversible, but with yet unclear pathophysiology. Reversible dilated cardiomyopathy is a rare disease with very few cases described in the literature (less than 10). The Case A 41–year–old man with a silent cardiological history (only cocaine and alcohol abuse in past) is admitted for visceral leishmaniasis. Cardiological evaluation: LBBB in ECG (none previous available); no abnormality detected on ECOCG (EF 55%). Ten days after the AmB cycle, onset of worsening dyspnoea needing hospital treatment after a further two weeks for heart failure (HF). At ECOCG severe left ventricular dysfunction (EF 30%), no rise of cardiac enzymes was detected. Coronary angiography showed 50–75% stenosis on RCA and LAD, treated by angioplasty and stenting. Cardiac MRI showed: dilated left ventricle with diffuse biventricular hypokinesis (FE 16% left and 22% right), areas of LGE of non–ischemic appearance. HFrEF GDMTs were prescribed, with progressive clinical improvement over the next four weeks; at cardiac MRI performed one month later, partially recovery of biventricular function (FE sn 41% right 48%) was found. The ECG showed regression of LBBB. No myocardial biopsy was performed, so it is not possible to get to an unequivocal cardiac dysfunction’s cause. However, the time relationship between the use of AmB and the clinical findings evolution, consistently with the few literature available, suggests a probable diagnosis of AmB toxic cardiomyopathy. An ischaemic cause of the dysfunction is unlikely by the MRI feature and by coronary angiography findings. Literature data suggest that the presence of predisposing factors for cardiac dysfunction, rather than the duration of treatment or preparation used, is the most relevant factor in the development of AmB–related cardiomyopathy. It’s important to perform cardiac monitoring in all patients receiving AmB therapy. In all reported cases, cardiac function recovered substantially after cessation of AmB treatment.

Minocycline-induced drug reaction with eosinophilia and systemic symptoms (DRESS) masquerading as acute leukemia.

Drug reaction with eosinophilia and systemic symptoms (DRESS) is an idiosyncratic drug reaction characterized by fever, rash, and lymphadenopathy associated with atypical lymphocytosis and eosinophilia. Visceral organ involvement is also seen and hence it often mimics hematolymphoid malignancies. A 19-year-old girl presented with generalized pruritic rash, fever, lymphadenopathy, and lymphocytosis. Subsequently, she developed respiratory distress with a fall in SpO2. Flow cytometry, bone marrow studies, and infectious workup were normal. Skin biopsy and clinical assessment criteria established the diagnosis of DRESS secondary to minocycline intake. Discontinuation of the offending drug is most important to abet the hypersensitivity reaction. Visceral organ involvement requires the use of steroids and immunosuppressive agents. Our patient responded well to treatment and is presently symptom-free and on follow-up for the last 6 months.

Outcomes of posterior sheath supplementation with Vicryl mesh in TAR-a single-center study.

In the Transversus Abdominis Release (TAR) procedure, ideally, the posterior sheath is completely reapproximated to establish an interface isolating the polypropylene mesh from visceral contents. When primary closure of the posterior sheath is unachievable, Vicryl mesh is commonly used to supplement the posterior sheath closure and an uncoated polypropylene mesh is placed superficial to the Vicryl mesh. The long-term implications of utilizing Vicryl mesh as an antiadhesive barrier are poorly understood. In this study, we aimed to assess our outcomes when utilizing Vicryl mesh to supplement the posterior sheath defects when placed underneath polypropylene mesh in patients undergoing posterior component separation. Adult patients who underwent VHR with concurrent TAR procedure with a permanent synthetic mesh and posterior sheath supplementation with Vicryl mesh in the Cleveland Clinic Center for Abdominal Core Health between January 2014 and December 2022 were queried retrospectively from a prospectively collected database in the Abdominal Core Health Quality Collaborative. We evaluated 30-day wound morbidity, perioperative complications, long-term mesh-related complications, and pragmatic hernia recurrence. 53 patients who underwent TAR procedure with posterior sheath supplementation using Vicryl mesh and had a minimum 12-month follow-up were identified. Of the53 patients, 94.3% presented with recurrent hernias, 73.6% had a midline hernia, 7.5% had a flank hernia, and 18.9% had concurrent parastomal hernia. The mean hernia width was 24.9 cm (± 8.8 cm). No Vicryl mesh-related operative complications were identified in our study, with no instances of mesh erosion, fistulas, or interventions for small bowel obstruction. Skin necrosis requiring reoperations was observed in three patients (5.7%), leading to permanent mesh excision in two cases (3.8%) without intraabdominal visceral involvement. Throughout the 12-month follow-up, 23 incidences (43.4%) of surgical site occurrences (SSOs) and surgical site occurrences requiring procedural intervention (SSOPI) were documented. Our findings suggest that posterior sheath supplementation with Vicryl mesh is a feasible approach to achieve posterior sheath closure in challenging abdominal wall reconstruction cases. Given the absence of notable mesh-related complications and a similar hernia recurrence rate to cases without posterior sheath supplementation, Vicryl mesh can be used to safely achieve posterior sheath closure in complex reconstructions with insufficient native tissue.

Abstract PO4-10-04: Treatment differences by race and age in metastatic hormone receptor-positive/HER2-negative breast cancer

Abstract Introduction: Black and younger patients are more likely to have aggressive forms of breast cancer. Endocrine therapy (ET) plus a CDK4/6 inhibitor is the standard of care first-line therapy for patients with hormone receptor-positive, HER2-negative (HR+/HER2-) metastatic breast cancer (MBC). Recent data has shown better outcomes with this approach compared to chemotherapy, even for patients with aggressive disease. Our study looked at differences in first-line treatment among Black and younger women with HR+/HER2- MBC. Methods: Clinical characteristics, treatment, and outcomes of patients diagnosed with HR+/HER2- MBC between 2011-2022 were retrieved from the UNC Metastatic Breast Cancer Database. Log binomial regression modeling compared treatment choices by group, and Cox proportional hazards regression modeling evaluated progression-free survival (PFS) from the start of treatment. Results: 524 patients were included in this analysis. 30% were young patients (&amp;lt; 50 years of age), 20% were Black patients, 62% had only 1 site of metastasis and 51% had visceral involvement. When looking at first-line treatment for metastatic disease, 21% of overall patients had received chemotherapy. The likelihood of receiving chemotherapy was higher for younger verses (vs) older patients (29% vs 18%, RR=1.63, p=0.004), for Black vs White patients (31% vs 18%, RR=1.71, p=0.002), and for those with visceral vs non-visceral involvement (26% vs 16%, RR=1.67, p=0.004). A model including age, race, and visceral involvement showed similar findings. Among patients who received ET as the first line treatment for metastatic disease, the likelihood of receiving CDK 4/6 inhibitors in addition to ET was lower for young Black patients compared to young White patients (41% vs 74%, RR=0.55, p=0.02). However, among older patients &amp;gt;=50, no significant difference was seen by race (Blacks 60% vs Whites 56%, RR=1.1, p=0.61). Adjusting for visceral involvement showed similar findings. Patients who received ET (with or without CDK 4/6 inhibitors) had better PFS compared to patients receiving chemotherapy as first-line therapy (HR 0.65, 95% CI 0.49, 0.88, p=0.005), this held true after adjusting for age, race, treatment group and visceral involvement (HR 0.7, p=0.02). A stratified analysis showed similar findings within Black patients (HR 0.42, p=0.003), and young patients (HR 0.55, p=0.01). Conclusion: Overall, Black and younger patients were more likely to receive chemotherapy as the first-line treatment for metastatic disease. Among patients who received ET as the first-line treatment for MBC, young Black patients were less likely to receive CDK 4/6 inhibitors compared to young White patients. Further studies are needed to outline the multi-level factors contributing to the identified disparities in care among patients with HR+/HER2- MBC. Citation Format: Yara Abdou, Joannie Ivory, Allison Deal, Ally Wardell, Amy Wheless, Claire Dees, Lisa Carey. Treatment differences by race and age in metastatic hormone receptor-positive/HER2-negative breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-10-04.

Abstract PO4-13-12: PIK3CA mutational status in tissue &amp; plasma as a prognostic tool in HR+/HER2- breast cancer (BC)

Abstract Background: Activating mutations of PIK3CA gene are described in about 30-40% of BC. They confer overall worse prognosis and resistance to endocrine and chemotherapeutic therapy. Concordance between testing methods (tissue &amp; plasma) are not widely studied. We aim to correlate tissue &amp; plasma assays and to analyze the discordant cases and prognostic value of PIK3CA mutations (PIK3CAm) in HR+/HER2- BC. Methods: We performed a retrospective and unicentric analysis of PIK3CA mutational status in tissue &amp; plasma samples in patients (pts) with HR+/HER2- BC from February/21 to April/23. PIK3CA test: Cobas®PIK3CA Mutation Kit. We correlated both diagnostic methods. Kaplan-Meier and Cox models were used to analyze progression-free survival (PFS) and comparison outcomes in PIK3CAm vs wild-type (wt). Results: We analyzed 225 samples from 161pts with HR+/HER2- BC (149 in tissue &amp; 76 in plasma). PIK3CA mutations were detected in 62pts (38.5%), of which 39.6% (59pts) were detected in tissue and 11.8% (9pts) in plasma. Hotspot mutations: H1047X (45.7%), E545X (20%) and E542K (12.8%). In advanced disease, metastatic BC (mBC), tissue &amp; plasma concordance was conducted in 64 cases, with overall correlation rate of 70.3%. We found PIK3CAm in 28pts: by both methods in 9pts (32.1%) and exclusively tissue detection in 19 cases (67.8%). Plasma detection was correlated with the presence of ≥3 metastatic sites (66.7% vs 31.6%; p=0.08) and with collection of samples during disease progression (66.7% vs 47.4%; p=0.43). 80pts received treatment with CDK4/6 inhibitors + endocrine therapy. PFS was slightly shorter in PIK3CAm vs wt (24m vs 30m; HR=1.39 [95%CI,0.7-2.4], p=0.26). A sub-analysis was performed based on exons 9 &amp; 20, showing a significantly lower PFS in PIK3CAm exon 9 vs 20 population (9.7m vs 30.3m; HR=2.84 [95%CI,1.1-7.4], p=0.02). In addition, plasma detection of PIK3CAm was associated with worse PFS compared with PIK3CAm detected only in tissue (12.4m vs 29.3; HR=2.4 [95%CI,0.8-6.5], p=0.08). Although we observed a trend towards a poorer PFS in pts with visceral involvement in PIK3CAm (21.9m vs 30.1m; HR=2.82 [95%CI,0.6-12.3], p=0.14), in a multivariate analysis, mutations in exon 9 were an independent poor prognostic factor regardless visceral involvement and detection in plasma; p=0.05. Conclusions: Our results support the PIK3CA determination in tissue as the diagnostic method of choice, although further studies could better define the role of liquid biopsy in the detection of PIK3CAm. In our population, the presence of PIK3CAm confers poorer prognosis in luminal BC, being significantly worse in mutation carriers in exon 9 regardless visceral involvement and plasma mutation detection. Table. Tissue &amp; plasma correlation in patients with PIK3CA mutational status tested in our population (mBC). Citation Format: Eduardo Terán Brage, Rebeca Lozano Mejorada, Aline Rodrigues Françoso, José Antonio Muñóz Leon, Álvaro López Gutiérrez, Luis Figuero-Pérez, Daniel Morchón Araujo, María Garijo Martínez, Jonnathan Roldán Ruiz, María Mar Abad Hernández, Magdalena Sancho de Salas, Emilio Fonseca Sánchez, César Augusto Rodríguez Sánchez. PIK3CA mutational status in tissue &amp; plasma as a prognostic tool in HR+/HER2- breast cancer (BC) [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-13-12.

Abstract PO3-06-01: Factors associated with first- and second- line attrition among metastatic breast cancer patients

Abstract Background: Estimating patient attrition across lines of treatment, i.e., the probability that upon failing one treatment the patient will be able to receive a subsequent treatment, may be a valuable tool for treatment sequencing. We sought to describe first-to-second line (1to2-line) and second-to third line (2to3-line) attrition rate and factors associated with attrition. Methods: The GIM14/BIO-META is an ongoing, ambispective observational multicenter study enrolling breast cancer patients receiving first-line therapy. In progressing patients, attrition was defined as no further anticancer treatment and death within 6 months from the end of the previous line. Attrition from 1to2-line and from 2to3-line was studied by descriptive analyses, factors associated with attrition by univariate ad multivariable logistic models. Results: From January 2000 to December 2021, 3,109 patients with metastatic breast cancer were enrolled in the GIM14/BIO-META study. After the exclusion of 611 patients with ongoing first-line treatment, we included 2,498 patients in the analysis of 1to2-line attrition. Considering tumor subtype, 1,650 (66.0%) patients were diagnosed with metastatic luminal-like, 622 (24.9%) with HER2-positive and 177 (7.1%) with triple negative (TN) tumors. At the time of diagnosis of advanced disease, almost half of the patients (52.0%) had only one involved metastatic site and 45.9% of the patients were diagnosed with visceral involvement. Overall, 1to2-line attrition was 9.0% (224/2,498) with similar attrition for patients with luminal-like (8.5%) and HER2-positive (7.1%) breast cancer. Patients with TN disease experience the highest 1to2-line attrition (13.0%). Age, disease-free interval from primary tumor diagnosis, and type of metastatic spread independently predicted 1to2-line attrition. Univariate analyses of factors associated with 1to2-line attrition among patients with luminal-like breast cancer were similar to those of the entire cohort. Overall, 2to3-line attrition was 14.0% (260/1,861) with higher attrition rates among patients with TN disease (22.7%) compared to patients with luminal-like (13.4%) and HER2-positive (13.0%) breast cancer. Age, tumor subtype, pattern of visceral spread and shorter time-to treatment discontinuation during first-line therapy were independent factors associated with 2to3-line attrition. Conclusions: Pending confirmation in independent series and integration with biomarkers of treatment failure, these results, may provide a valuable support for treatment decisions and clinical research on treatment sequencing. Citation Format: Eva Blondeaux, Luca Boni, Giovanna Chilà, Arianna Dri, Roberta Caputo, Francesca Poggio, Alessandra Fabi, Grazia Arpino, Federico Pravisano, Elena Geuna, Tommaso Ruelle, Irene Giannubilo, Michelino de Laurentiis, Fabio Puglisi, Claudia Bighin, Matteo Lambertini, Filippo Montemurro, Lucia Del Mastro. Factors associated with first- and second- line attrition among metastatic breast cancer patients [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-06-01.