Site Of Relapse Research Articles

Intracranial Relapse in Pediatric Sarcoma.

Advances in local control techniques, chemotherapy regimens, and imaging modalities have led to improvements in both morbidity and mortality in pediatric sarcoma patients. However, approximately one-third of patients develop disease relapse and intracranial metastasis was considered rare. The incidence of sarcoma brain metastasis is thought to have increased and is associated with grim outcomes. This was a retrospective study of 3 deidentified patient charts illustrating the possibility of the central nervous system as a potential site for pediatric sarcoma relapse and investigate the patterns of such relapses. We note this is the first report of infantile fibrosarcoma brain metastasis and a rare report of sarcoma lymph node metastasis. In addition, each patient was treated with targeted therapies, including entrectinib, Ruxolitnib, and pazopanib. Caregivers in cases 2 and 3 reported new-onset neurological manifestations before identification of new brain metastasis, indicating a lag in detection of new intracranial relapse in asymptomatic sarcoma patients. We suggest implementing a brief review of systems screening tool focused on concerning neurological manifestations to screen for new brain metastasis.

The dynamics of HER2-low expression during breast cancer progression.

Low HER2 expression is emerging as an actionable target for the treatment of breast cancer (BC) with the antibody drug conjugate Trastuzumab deruxtecan. The aim of the study was to characterize the dynamics of HER2 expression during BC progression. We evaluated the evolution of HER2 expression in 171 paired primary and metastatic BCs (pBCs/mBCs) by including the HER2-low category. The proportions of HER2-low cases were 25.7% in pBCs and 23.4% in mBCs, respectively, while those of HER2-0 cases were 35.1% and 42.7%, respectively. The overall conversion rate between HER2-0 and HER2-low was 31.7%. HER2-low switching to HER2-0 was more frequent than the reverse (43.2% vs. 23.3%; P = 0.03). Two (3.3%) and 9 (20.5%) cases of pBCs with a HER2-0 and a HER2-low status, respectively, were converted to HER2-positive mBCs. In contrast, 10 (14.9%) HER2-positive pBCs were converted to HER2-0 and an identical number to HER2-low mBCs, respectively, significantly higher than that when compared to the HER2-0 to HER2-positive (P = 0.03), but not HER2-low to HER2-positive conversion. No significant difference was found when comparing the conversion rates among the common organs of relapse. Of the 17 patients with multiorgan metastases, 41.2% had discordance among the different sites of relapse. HER2-low BCs constitute a heterogeneous group of tumors. Low HER2 expression is dynamic, with significant discordance between primary tumors and advanced disease as well as the distant sites of relapse. Repeat biomarker studies from advanced disease are warranted in making appropriate treatment plans in the pursuit of precision medicine.

What happens to children with acute lymphoblastic leukemia in low- and middle-income countries after relapse? A single-center experience from India

Managing a child with acute lymphoblastic leukemia (ALL) after relapse is arduous in low- and middle-income countries. A file review of children aged ≤15 years diagnosed with relapsed ALL from 2010 to 2019 was performed. Classification of relapse followed the Berlin-Frankfurt-Münster (BFM) scheme. The majority of patients were treated with a modified ALL-REZ-BFM protocol. Of 764 children treated for ALL in the study period, 163 (21.3%) relapsed. The median age at relapse was 101 months (range: 8–297). The immunophenotype was B-ALL and T-ALL in 140 (86%) and 23 (14%) patients. The site of relapse was extramedullary, combined, and medullary in 46 (28%), 45 (28%), and 72 (44%) patients. Very early, early, and late relapses were observed in 57 (35%), 66 (40%), and 40 (25%) patients. The proportions of extramedullary and medullary sites were greater among patients with early and late relapses, respectively (p = 0.039). Eighty-four (52%) patients were treated with palliative intent. The 2-year event-free survival (EFS) of patients treated with curative intent was 36.3 ± 6.3%. The 2-year EFS for very early/early and late relapses were 18.2 ± 6.2% and 67.6 ± 10.4% (p < 0.001). The 2-year EFS did not differ between extramedullary, combined, and medullary relapses. Treatment-related mortality occurred in 14 (20%) patients. More than 50% of the patients with relapse were treated with the intent of palliation. Extramedullary relapses were more likely to be early and did not have a better outcome than medullary relapses. Children with late relapse had a fair chance of survival with chemotherapy.

Prostate-specific membrane antigen positron emission tomography detected local failure after post-prostatectomy radiation therapy: Low rates of out-of-field recurrence validates current Australian prostate bed contouring guidelines.

The Australian Faculty of Radiation Oncology Genitourinary Group (FROGG) developed prostate bed clinical target volume (CTV) contouring guidelines which were subsequently used to develop the National EviQ guidelines for adjuvant and salvage post-prostatectomy radiotherapy (PPRT). These guidelines were based mainly upon consensus agreement. With the advent of prostate-specific membrane antigen (PSMA) positron emission tomography (PET), sites of recurrence can now be detected with low prostate-specific antigen (PSA) levels following radical prostatectomy. We evaluated sites of recurrence in patients treated with FROGG/EviQ CTVs to inform upcoming modifications of these guidelines. At our institution, we use the FROGG/EviQ guidelines for PPRT. From 2015, patients with PSA failure following PPRT have been re-staged using PSMA PET imaging. We identified patients with PET-avid local, nodal, and distant recurrences, fusing them with original treatment plans to determine whether recurrences were within or outside the prostate bed CTV. Regional nodal failures were reviewed to determine if they were within current elective node contouring guidelines. Ninety-four patients had positive PSMA PET following PPRT. Nine (9.6%) recurrences were local, seven being local-only. One local recurrence (1.1%) was just superior to the contoured prostate bed CTV, located within the vas deferens. Seventy-three (77.7%) patients had a component of node failure, with 56 (59.6%) having node-only failure. Sites of nodal relapses were covered by standard contouring guidelines 60.3% of the time. The low recurrence rate outside of current prostate bed CTV contouring guidelines is consistent with other studies using contemporary contouring, and validates the efficacy of the current FROGG/EviQ prostate bed CTV definition.

Patterns of Relapse in Australian Patients With Clinical Stage 1 Testicular Cancer: Utility of the Australian and New Zealand Urogenital and Prostate Cancer Trials Group Surveillance Recommendations.

International guidelines advocate for active surveillance as the preferred treatment strategy for patients with stage 1 testicular cancer after orchidectomy although a personalized discussion is required. We conducted an analysis of individuals registered in iTestis, Australia's testicular cancer registry, to describe the patterns of relapse and outcomes of patients treated in Australia where the Australian and New Zealand Urogenital and Prostate Cancer Trials Group Surveillance Recommendations are widely adopted. A total of 650 individuals diagnosed between 2000 and 2020 were included, 63% (411 of 650) seminoma and 37% (239 of 650) nonseminoma. The median age was 34 years (range 14-74). 26% (106 of 411) with seminoma and 15% (36 of 239) nonseminoma received adjuvant chemotherapy. After a median follow-up of 43 months (range 0-267) postorchidectomy, relapse occurred in 10% (43 of 411) of seminoma and 18% (43 of 239) of nonseminoma. The two-year relapse-free survival was 92% (95% CI, 89 to 95) and 82% (95% CI, 78 to 87) in seminoma and nonseminoma, respectively. All relapses (86 of 86) were detected at a routine surveillance visit; 98% (85 of 86) were asymptomatic and detected solely through imaging (62 of 86, 72%), tumor markers (6 of 86, 7%), or a combination (17 of 86, 20%). The most common relapse site was isolated retroperitoneal lymphadenopathy (53 of 86, 62%). No nonpulmonary visceral metastases occurred. At relapse, 98% (84 of 86) had International Germ Cell Cancer Collaborative Group (IGCCCG) good prognosis; 2 of 86 intermediate prognosis (both nonseminoma). No deaths occurred. In our cohort of stage 1 testicular cancer, where national surveillance recommendations have been widely adopted, recurrences were detected at routine surveillance visits and, almost exclusively, asymptomatic with IGCCCG good-prognosis disease. This provides reassurance that active surveillance is safe.

Patterns of recurrence post prostatectomy in the PSMA era: What lessons can we take to daily practice from a high-volume nuclear medicine center?

e17013 Background: PSMA has deeply modified the treatment of prostate cancer, mainly in the biochemical recurrence setting, where the therapeutic plan may be changed in up to two thirds of cases. Unfortunately, this diagnostic tool is still not fully available in many places over the world. Growing evidence from high-volume nuclear medicine centers may guide the development of adapted treatment plans based on sites of relapse according to wide available clinical information. Methods: We retrospectively reviewed 648 Ga68-PSMA-PET-CT scans in the biochemical relapse setting in patients initially treated with prostatectomy. Results were classified either as negative or positive if abnormal SUV uptake was detected in the prostate bed, pelvis, or distant organs. We then classified the patients with positive tests based on sites of relapse according to serum PSA level. Results: Among the 648 analyzed patients, there were 60, 63, and 61 recurrences in prostate bed, pelvis, or distant organs, respectively. For those with serum PSA ≤ 1.0 ng/mL, there was a higher chance of locoregional failure (prostate bed or pelvis), with less than 20% presenting distant metastasis. When assessing patients with serum PSA 1.1-2.0 ng/mL, the rate of distant metastasis increased to 22.7%, while it was found in 40.7% of patients with serum PSA between 2 and 5 ng/mL. Conclusions: PSMA-PET-CT scan is clearly modifying the therapeutic landscape of prostate cancer in different scenarios. Although it is not available in many regions due to high financial costs and logistic barriers, the emerging evidence arising from specialized cancer centers matching the clinical information with tests results may help doctors to make better treatment decisions even without PSMA-PET-CT scans. [Table: see text]

The Ave-Rec trial: Phase II trial of PD-L1/PD-1 blockade with avelumab plus chemoradiotherapy for locally advanced resectable T3B-4/N1-2 rectal cancer—Toxicity and interim efficacy data.

3616 Background: Neoadjuvant long course chemoradiotherapy (LCCRT) for locally advanced rectal cancer (LARC) results in a complete pathological response rate in 10-30% of patients (pts), but with 20-40% non-responders and 10-15% have local recurrence. Radiotherapy (RT) is immuno-stimulatory by enhancing local/distant tumour cell death, but also immunosuppressive as it stimulates PDL1 production and myeloid-derived suppressor cell activity. Hence PDL1 inhibition may be required to enhance the immuno-stimulatory effects of RT. Hypothesis: In pts with resectable LARC, the anti-PDL1 antibody Avelumab given post LCCRT may enhance the pathological/imaging response rates whilst reducing local/distant relapse rates. Methods: Phase II single arm trial. All pts had standard LCCRT (50.4Gy RT plus 5FU [225mg/m2/day/CI] or Capecitabine [825mg/m2 BID on days of RT] over 5.5 weeks). Post LCCRT (prior to surgery), pts received 4 cycles Avelumab (AV) (10mg/kg, q2 weeks), then surgical resection at 10-12 weeks post LCCRT. Fresh tumour biopsy and ctDNA sampling taken pre LCCRT, pre Cycle 1 AV and at surgery. Response by FDG PET/CT and pelvic MRI at 8 weeks post LCCRT, pre surgery. Inclusion Criteria: pts with LARC (MRI stage T3b-4/N1-2/M0), planned for LCCRT followed by curative resection, tumoural lower border within 12cm from anal verge, measurable disease (RECIST1.1), ECOG 0-1, adequate organ function and no contraindications to AV therapy. Endpoints: (a) Primary; Complete pathological response rate post-LCCRT (Target ≥ 35%), documented by central pathologist, (b) Secondary; MRI and FDG PET/CT imaging responses by RECIST1.1 and PERCIST, respectively. Toxicity. (c) Exploratory; Tumoural immune cell subsets/checkpoint expression (by multiplex immunohistochemistry and in-vitro functional assays) and ctDNA analysis. Distant relapse-free survival and the sites of relapse. ANZCTR : NCT03299660. Results: 37 pts across 6 sites, with 33 patients (89%) received allocated interventions: LCCRT, AV and surgery (where possible). Age median 55 years (31-76). M:F 23:10. Baseline tumoural stage: T3b-d 75%, T4a-b 25%. No pts with dMMR/MSI-H tumour. Overall 33 pts completed LCCRT, 31 pts (83%) completed all 4 cycles of AV and 32 pts (86%) had planned surgery (22, ULAR, 2 APR, 2 AR, 6 Other). ORR Pelvic MRI presurgery (N = 33): 2 CR, 14 PR, and 31 DCR. FDG PET/CT (N = 31): 10 CMR, 18 PMR and 3 SMD. Overall 10 pts Grade 3/4 AEs, with 15 G3/4 events. Only 3 pts with treatment-related G3 and no G4 AEs. No specific immune-related G3 AEs observed. Post-operative complications were not unexpected. Conclusions: Consolidation Avelumab post LCCRT for pts with LARC, was well tolerated with promising activity. Pathological response, biological substudies (immunological and ctDNA) and survival endpoints to be reported. Clinical trial information: NCT03299660 .

Role of genomics in intrahepatic cholangiocarcinoma for liver-directed therapy

Only a minority of patients with intrahepatic cholangiocarcinoma are candidates for curative resection. Even those with disease limited to the liver may not be surgical candidates due to patient, liver, and tumor factors, including comorbidities, intrinsic liver disease, inability to establish a future liver remnant, and tumor multifocality. In addition, even after surgery, recurrence rates are high, with the liver being a predominant site of relapse. Lastly, tumor progression in the liver can sometimes result in demise for those with advanced disease. Therefore, it is not surprising that non-surgical, liver-directed therapies have emerged as both primary and complementary treatments for intrahepatic cholangiocarcinoma for multiple stages. Liver-directed therapies can be performed directly into the tumor via thermal or non-thermal ablation, catheter-based infusion into the hepatic artery containing either cytotoxic chemotherapy or radioisotope bearing spheres/beads, or delivered via external beam radiation. Presently, these therapies' selection criteria have been based on tumor size, location, liver function, and referral to particular specialists. In recent years, molecular profiling of intrahepatic cholangiocarcinoma has revealed a high rate of actionable mutations, and several targeted therapies have been approved for treatment in the second-line metastatic setting. However, little is known about these alterations' role in localized disease treatments. Therefore, we will review the current molecular landscape of intrahepatic cholangiocarcinoma and how it has been applied to liver-directed therapy.

Prognostic and clinical impact of the endocrine resistance/sensitivity classification according to international consensus guidelines for advanced breast cancer: an individual patient-level analysis from the Mammella InterGruppo (MIG) and Gruppo Italiano Mammella (GIM) studies

Prior exposure to adjuvant endocrine therapy (ET) and timing to recurrence are crucial factors for first-line treatment choices in patients with hormone receptor-positive/HER2-negative (HR+/HER2-) breast cancer (BC) and in clinical trial eligibility, classifying metastatic HR+/HER2- BC as endocrine sensitive (ES) or primary (1ER)/secondary (2ER) resistant. However, this classification is largely based on expert opinion and no proper evidence exists to date to support its possible prognostic and clinical impact. This analysis included individual patient-level data from 4 adjuvant phase III randomized trials by the Mammella InterGruppo (MIG) and Gruppo Italiano Mammella (GIM) study groups. The impact of endocrine resistance/sensitivity classification on overall survival (mOS, defined as time between date of distant relapse and death) was assessed in both univariate and multivariate Cox proportional hazards models. Between November 1992 and July 2012, 9058 patients were randomized in 4 trials, of whom 6612 had HR+/HER2- BC. Median follow-up was 9.1 years (interquartile range [IQR] 5.6-15.0). In the whole cohort, disease-free survival and OS were 90.4% and 96.6% at 5 years, and 79.1% and 89.4% at 10 years, respectively. The estimated hazard of recurrence raised constantly during the first 15 years from diagnosis, being more pronounced during the first 2 years and less pronounced after year 7. Among the 493 patients with a distant relapse as first disease-free survival event and available date on ET completion, 72 (14.6%), 207 (42.0%) and 214 (43.4%) were classified as having 1ER, 2ER and ES, respectively. Median follow-up from diagnosis of a distant relapse was 3.8 years (IQR 1.6-7.5). Patients with 1ER were significantly more likely to be younger, to have N2/N3 nodal status, grade 3 tumours and to develop visceral metastases. Site of first distant relapse was significantly different between the 3 groups (p=0.005). In patients with 1ER, 2ER and ES breast cancer, median mOS was 27.2, 38.4 and 43.2 months, respectively (p=0.03). As compared to patients with ES disease, a higher risk of death was observed in those with 1ER (adjusted Hazard Ratio [aHR] 1.54; 95% CI 1.03-2.30) and 2ER (aHR 1.17; 95% CI 0.87-1.56) (p=0.11). This large analysis with long-term follow-up provides evidence on the prognostic and clinical impact of the currently adopted endocrine resistance/sensitivity classification in patients with HR+/HER2- advanced BC. This classification may be considered a valid tool to guide clinical decision-making and to design future ET trials in the metastatic setting. AIRC.

Radiotherapy-Dose Escalated for Large Volume Primary Tumors-And Cetuximab with or without Induction Chemotherapy for HPV Associated Squamous Cell Carcinoma of the Head and Neck-A Randomized Phase II Trial.

Eligible patients in this multicenter, randomized, controlled, phase 2 trial had p16-positive locoregionally advanced SCCHN. Patients were randomized in a 1:1 ratio to either RT with cetuximab (arm B) versus the same regimen preceded by two cycles of taxotere/cisplatin/5-FU (arm A). The RT dose was escalated to 74.8 Gy for large volume primary tumors. Eligibility criteria included patients of 18-75 years, an ECOG performance status 0-1, and adequate organ functions. From January 2011 to February 2016, 152 patients, all with oropharyngeal tumors were enrolled, 77 in arm A and 75 in arm B. Two patients, one in each group, withdrew their consent after randomization, leaving 150 patients for the ITT analysis. PFS at 2 years was 84.2% (95% CI 76.4-92.8) in arm A and 78.4% (95% CI 69.5-88.3) in arm B (HR 1.39, 95% CI 0.69-2.79, p = 0.40). At the time of analysis, there were 26 disease failures, 9 in arm A and 17 in arm B. In arm A, 3 patients had local, 2 regional, and 4 distant relapses as first sites of recurrence, and in arm B, 4, 4, and 9 relapses in corresponding sites. Eight out of 26 patients with disease progression had salvage therapy and 7 were alive NED (no evidence of disease), at 2 years. Locoregional control was 96% in arm A and 97.3% in arm B and OS 93% and 90.5%, respectively. Local failure as first site of recurrence was low, in 4.6% of patients and was similar for T1/T2 and T3/T4 tumors (n.s). Nevertheless, out of 7 patients with primary local failures, 4 were treated with the escalated RT dose. Toxicity was low and similar in the treatment arms. There was one fatal event in arm A where the combined effects of the drugs used in chemotherapy and cetuximab could not be ruled out. PFS, locoregional control and toxicity did not differ between the two arms, OS was high, and there were few local relapses. In arm B, more than twice as many patients had distant metastasis as the first site of relapse compared to arm A. The response to IC was found to define 29% of patients in arm A who did not have a tumor relapse during follow-up. An escalated dose of 74.8 Gy could mitigate the negative impact of large tumor volume but for some patients, even this intensified treatment was insufficient.

Predictors of Relapse and Survival in Testicular Germ cell Tumors in Children

Background: Testicular germ cell tumors are common solid organ malignancies in children with a survival rate of more than 90 %. This study aims to assess the predictors of relapse and survival in testicular germ cell tumors in children.&#x0D; Methodology: A retrospective review was conducted on children up to the age of 18-years from January 2010 to December 2020 with a diagnosis of primary testicular germ cell tumors. Factors related to relapse and survival like age, baseline levels of tumor markers in serum and on relapse, stage at diagnosis, histological type, tumor laterality &amp; size of the tumor in testicular germ cell tumors were analyzed. The data was entered into SPSS version 20. Statistical significance was set at a p-value ≤0.05.&#x0D; Results: A total of 115 patients with a mean age of 5.42+ 1.54 years having testicular germ cell tumor were treated. Seventeen patients (14.7 %) had relapse of disease. Relapse was highest in patients with stage I disease (64.7 %). Yolk sac tumor was the most common pathology that was noted in twelve (70 %) patients. The most common site of relapse was the retroperitoneum (70 %). Age of patient, stage of disease, and lymphovascular invasion were significant predictors of relapse and survival in testicular germ cell tumors.&#x0D; Conclusion: Management of patients with testicular germ cell tumors requires standardized follow-up protocol for early detection and treatment of disease relapse. Complete surgical excision with meticulous control of the residual disease is critical to prevent disease relapse.&#x0D; Keywords: Chemotherapy, Children, Outcome, Relapse, Testicular Tumor&#x0D; &#x0D;

Time to dismiss boost? Outcomes of children with localized and metastatic germinoma

To determine long-term outcomes of a cohort of children with germinoma treated with chemotherapy and radiation therapy without primary tumor boost even in the absence of complete response to chemotherapy METHODS: This retrospective study analyzed the outcome of patients with germinoma consecutively diagnosed and treated at a tertiary care center from January 2000 to December 2021. MRIs were reviewed by two radiologists, blinded to patient data. Tumor location at diagnosis, tumor response to chemotherapy and at completion of radiation therapy and site of relapse were assessed. Tumor response was assessed radiologically by determining the tumor size and response on diffusion-weighted imaging, in addition to biochemical, cytological parameters and neurological status. Of 46 pediatric germinoma patients, 29 children (14 male; median age 12.8years) received no primary tumor boost. Median follow-up was 63months (range 9-187months). Twenty-five children had localized disease and tumor location was suprasellar (n = 11), pineal (n = 10), bifocal (n = 3) and basal ganglia (n = 1) while 4 children had metastatic disease at presentation. All patients completed multi-agent chemotherapy followed by either ventricular irradiation (VI) (23.4Gy) (n = 23), whole brain (WBI) (23.4Gy) (n = 5) or craniospinal radiation (CSI) (23.4Gy) (n = 1). Two children, who had localized disease at presentation and received VI after chemotherapy, relapsed 9months and 32months after completion of treatment respectively. No patient had a local relapse. Location of relapse was distant, outside (n = 1) and out- andinside (n = 1) the irradiation field. Five-year progression free survival (PFS) was 91% and overall survival (OS) was 100%. In this case series, excellent 5-year PFS and OS rates were achieved with chemotherapy followed by radiation therapy of 23.4Gy delivered without primary tumor boost. No local relapse was observed despite omitting primary tumor boost in patients with localized and metastatic germinoma.

MP33-01 RISK OF RESIDUAL TERATOMA AFTER COMPLETE RESPONSE FOLLOWING FIRST-LINE CHEMOTHERAPY IN MEN WITH METASTATIC NON-SEMINOMATOUS GERM CELL TUMOR AND IGCCCG INTERMEDIATE/POOR PROGNOSIS: A MULTI-INSTITUTIONAL RETROSPECTIVE COHORT STUDY

MP33-01 RISK OF RESIDUAL TERATOMA AFTER COMPLETE RESPONSE FOLLOWING FIRST-LINE CHEMOTHERAPY IN MEN WITH METASTATIC NON-SEMINOMATOUS GERM CELL TUMOR AND IGCCCG INTERMEDIATE/POOR PROGNOSIS: A MULTI-INSTITUTIONAL RETROSPECTIVE COHORT STUDY

Description of a Retrospective Cohort of Epithelial Ovarian Cancer Patients with Brain Metastases: Evaluation of the Role of PARP Inhibitors in this Setting

The incidence of brain metastases (BM) in patients with epithelial ovarian cancer (EOC) is low: 0.3-11%. The onset of BM has been regarded as a late event with limited treatment options and poor prognosis. This retrospective case series aims to explore the current management strategies with particular emphasis on the use of PARP inhibitors and outcomes, as well as identification of other prognostic indicators. A total of 39 ovarian cancer patients with brain metastases were identified from eight cancer centres in the UK. Clinical characteristics, details of management, and survival data were collected. A total of 14/39 had BM as their first site of relapse. The majority (29 patients) received systemic treatments in addition to local radiotherapy (RT)/surgery. Nineteen patients had BRCA mutations (one somatic), one had a RAD51C mutation, and eighteen were BRCA wild type; one was unknown. A total of 14/39 patients received maintenance PARP inhibitors. As is well known, patients who received PARPi had consistently better outcomes. This was no different for those who received PARPi as part of the management of their BM. Platinum sensitivity and receiving more than one modality of therapy (e.g., radiation +/- chemotherapy and PARPi) for BM were also good prognostic indicators. Median PFS/OS for those treated with chemotherapy and either RT or surgery, then PARP inhibitor maintenance, have not been reached after a median of 33 months follow up. As with abdominal relapse, maintenance treatment with PARP inhibitors also has a valuable role in managing BMs in EOC patients.

Choline PET/CT in recurrent prostate cancer.

Biochemical recurrence (BR) occurs in up to 40% of patients with prostate cancer (PCa) treated with primary radical prostatectomy (RP). Choline PET/CT may show, in a single-step examination, the site of tumor recurrence earlier than traditional imaging methods, particularly at low prostate-specific antigen (PSA) levels, thus influencing subsequent treatment. Patients with recurrent and non-metastatic prostate cancer (nmPCa), who were assessed with choline PET/CT, were included in the analysis. Based on imaging results, the following therapeutic strategies were chosen: radiotherapy to the prostatic bed, androgen deprivation therapy (ADT), and chemotherapy or stereotactic body radiotherapy (SBRT) to either the pelvic lymph nodes or distant metastases. We assessed the impact of age, PSA levels, Gleason score (GS), and adjuvant therapy on oncological outcomes. Data from 410 consecutive nmPCa patients with BR who underwent RP as primary treatment were analyzed. One hundred seventy-six (42.9%) patients had a negative choline PET/CT, and 234 (57.1%) patients resulted positive. In the multivariate analysis, only chemotherapy and PSA at recurrence were significant independent prognostic factors on overall survival (OS). In the PET-positive subgroup, the number of relapses, PSA post-prostatectomy, and chemotherapy impacted on OS. PSA (post-surgery and at recurrence) affected progression-free survival (PFS) in the univariate analysis. In the multivariate analysis, GS, the number of relapse sites, and PSA (post-surgery and at recurrence) were significant prognostic factors for disease-free survival (DFS). Choline PET/CT provides better accuracy than conventional imaging for the assessment of nmPCa with BR after prostatectomy, thereby enabling salvage strategies and improving quality of life.

Haploidentical vs. HLA-matched donor hematopoietic stem-cell transplantation for pediatric patients with acute lymphoblastic leukemia in second remission: A collaborative retrospective study of the Spanish Group for Bone Marrow Transplantation in Children (GETMON/GETH) and the Spanish Childhood Relapsed ALL Board (ReALLNet).

Studies addressing the role of haploidentical as alternative to HLA-matched donors for stem cell transplantation (SCT) often include patients with diverse hematological malignancies in different remission statuses. We compared outcomes of children with acute lymphoblastic leukemia (ALL) undergoing SCT in second complete remission (CR2) from haploidentical (n = 25) versus HLA-matched donor (n = 51). Patients were equally distributed across both groups according to age, immunophenotype, time to and site of relapse, relapse risk-group allocation, and minimal residual disease (MRD) before SCT. Incidence of graft failure, acute graft versus host disease (GVHD), and other early complications did not differ between both groups. We found no differences in overall survival (58.7% versus 59.5%; p = .8), leukemia free survival (LFS) (48% versus 36.4%; p = .5), event free survival (40% versus 34.4%; p = .69), cumulative incidence (CI) of subsequent relapse (28% versus 40.9%; p = .69), treatment related mortality (24% versus 23.6%; p = .83), CI of cGVHD (4.5% versus 18.7%; p = .2), and chronic GVHD-free and leukemia-free survival (44% versus 26.3%; p = .3) after haploidentical donor SCT. Chronic GVHD (HR = 0.09; p=.02) had protective impact, and MRD ≥ 0.01% before SCT (HR = 2.59; p=.01) had unfavorable impact on LFS. These results support the role of haploidentical donor SCT in children with ALL in CR2.

Primary Testicular Lymphoma: Single Center Experience.

Primary testicular lymphoma (PTL) is an exceedingly rare and aggressive form of non-Hodgkin's lymphoma; the most common subtype is diffuse large B-cell (DLBCL). Standard treatment includes orchiectomy, chemotherapy, central nervous system (CNS) prophylaxis, and prophylactic radiation to the contralateral testis. PTL can reoccur years after complete remission. Treatment to immune sanctuary sites, CNS and contralateral testis, is crucial in preventing relapse. There are limited data characterizing this entity and this study aimed to add to existing literature. This descriptive retrospective study characterized twelve patients with PTL from years 2010-2021 at Allegheny Health Network. Their demographic data, prognostic factors, treatment regimens, and relapse sites (if any) were tabulated. The mean progression-free survival (PFS) was calculated to describe our experience in treating PTL. Twelve patients were diagnosed with PTL; 10/12 (83.33%) patients were diagnosed with ABC PTL-DLBCL. Median age of diagnosis was 67 years. Eight of the 12 (66.66%) were African American, 4/12 (33.33%) were Caucasian. At the time of diagnosis, 8/12 (66.66%) patients presented with an elevated lactate dehydrogenase (LDH) and 8/12 (66.66%) presented with a left testicular mass. Most were treated with R-CHOP (9/12), intrathecal methotrexate (IT-MTX) (10/12), and radiation to the contralateral testis (9/12). Three of the twelve (25%) patients relapsed. Median time to relapse was 8 months. Mean PFS was 50.417 months. We discuss our experience in treating PTL with RCHOP, IT-MTX, and irradiation to the contralateral testis and add to the limited pre-existing data that exist.

Abstract PD15-06: PD15-06 Pathologic complete response and breast-conserving surgery are associated with improved prognosis in patients with early-stage triple-negative breast cancer treated with neoadjuvant chemotherapy

Abstract Background: Neoadjuvant chemotherapy (NACT) is standard of care for patients with triple-negative breast cancer (TNBC). Treatment response, especially pathologic complete response (pCR), is a strong predictive factor for treatment outcome. In the setting of up-front surgery, retrospective data have suggested improved outcome in patients with early TNBC that received breast-conserving surgery with adjuvant radiotherapy (BCT) as compared to mastectomy. Methods: We identified 2632 patients with early TNBC from the German Breast Group meta-database. Patients with cT1-2 cN0 and ypN0, available surgery and follow-up data were eligible for this project. A total of 1074 patients from 8 prospective NACT trials were analyzed. Endpoints of interest were locoregional recurrence as first site of relapse (LRR, other sites of recurrence were considered competing events), disease-free survival (DFS) and overall survival (OS); analyses were performed using univariate and multivariate Fine-Gray (for LRR) and Cox models including study, age, cT, surgery type and pCR. For the analyses including pCR as covariable, only patients at risk at the landmark time were evaluated. Results: Median age was 48 years, 69.6% of patients had cT2 tumors and 85.3% underwent BCS. Of the 1074 analyzed patients, 48.8% achieved pCR. After a median follow-up of 64 months, there were 94 (8.8%) locoregional events as first site of relapse. Upon univariate analysis, absence of pCR (hazard ratio [HR]=2.28; 95%CI 1.44-3.61; p&amp;lt; 0.001) and ypT-stage (ypT0/is vs. ypT1-3, HR=0.61; 95%CI 0.40-0.95; p=0.028) were significantly associated with LRR, while type of surgery, age and cT-stage were not. Upon multivariate analysis, absence of pCR was the only factor associated with increased risk of LRR (HR=2.22; 95%CI 1.38-3.58; p=0.001). Patients that underwent mastectomy (N=158) were significantly younger (age ≤ 50 years 72.8% vs. 59.9% for BCT [N=916]; p=0.002) DFS and OS was significantly better in patients who underwent BCT compared to mastectomy (DFS: HR=0.47; 95%CI 0.34-0.66; p&amp;lt; 0.001 and OS: HR=0.40; 95%CI 0.26-0.63; p&amp;lt; 0.001). In multivariate analysis, BCT was associated with a significantly better DFS and OS as compared to mastectomy (DFS: HR=0.51; 95%CI 0.36-0.72; p&amp;lt; 0.001; and OS HR=0.43; 95%CI 0.27-0.68; p&amp;lt; 0.001), whereas absence of pCR was associated with significantly worse DFS and OS (DFS: HR=2.43; 95%CI 1.78-3.31; p&amp;lt; 0.001; and OS: HR=3.15; 95%CI 1.94-5.10; p&amp;lt; 0.001). Conclusions: In this retrospective analysis from the GBG meta-database, treatment response, e.g. pCR, was the main determinant of locoregional recurrence in patients with early stage TNBC treated with NACT. BCT was associated with improved DFS and OS compared to mastectomy, which may at least in part reflect favorable patient selection. Citation Format: David Krug, Valentina Vladimirova, Michael Untch, Thorsten Kühn, Andreas Schneeweiss, Carsten Denkert, Beyhan Ataseven, Christine Solbach, Bernd Gerber, Hans Tesch, Michael Golatta, Sabine Seiler, Jörg Heil, Valentina Nekljudova, Sibylle Loibl. PD15-06 Pathologic complete response and breast-conserving surgery are associated with improved prognosis in patients with early-stage triple-negative breast cancer treated with neoadjuvant chemotherapy [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr PD15-06.

Abstract P2-11-12: Pattern of distant relapse according to intrinsic molecular subtype in patients with HER2-positive breast cancer: a combined analysis of ShortHER, CherLOB, and two institutional cohorts

Abstract Background: All intrinsic molecular subtypes are represented among HER2-positive breast cancer, with implications on clinical outcome and treatment sensitivity. The impact of molecular subtypes on the pattern and site of relapse is largely unexplored. Methods: 677 patients with HER2-positive early breast cancer from the Shorther trial (n=437), the CherLOB trial (n=84) and two Institutional cohorts (Istituto Oncologico Veneto IRCCS Padova n=39 and Hospital Clinic Barcelona n=117) were included. Only patients with available PAM50 intrinsic molecular subtyping were considered. We analyzed the incidence of distant relapse (at any site and at specific sites) as the first event. Cumulative incidence was estimated according to competing risk analysis (Fine and Gray’s method). Competing risk regression was used to calculate the subdistribution Hazard Ratios (subHR) and their 95% Confidence Interval (CI). Results: The distribution of molecular subtypes was: 130 LumA (19%), 75 LumB (11%), 347 HER2-e (51%), 46 Basal (7%), 79 Normal (12%). Median follow up was 8.4 years (95%CI 8.2-8.6). The 10-yr cumulative incidence rates of distant relapse as first event were: LumA 7.9%, LumB 14.8%, HER2-e 14.7%, Basal 15.5%, Normal 10.4% (HER2-e vs LumA: SubHR 2.21, 95%CI 1.05-4.64, p=0.037). Table 1 shows the 5-yr and 10-yr cumulative incidence rates of distant metastases at specific sites (as first event) according to intrinsic subtype. HER2-e enriched and Basal tumors were more prone as compared to other subtypes to develop brain and lung metastasis as first event, respectively. Isolated brain metastases without extracranial disease occurred only in patients with HER2-e tumors. All brain metastases as first event occurred within 5 years from diagnosis. Bone-only disease as first event was less frequent in HER2-e and Basal subtype (subHR HER2-e vs LumA: 0.32, 95%CI 0.10-10.4. p=0.058). Next, we analyzed the frequency of site-specific first metastasis among patients who experienced a distant metastasis as first event (n=77). Lung metastases were more frequent in Basal tumors (LumA 25.0%, LumB 20.0%, HER2-e 24.4%, Basal 71.4%, Normal 0.0%, p=0.037) and bone metastases were more frequent in Luminal tumors (LumA 100.0%, LumB 60.0%, HER2-e 31.1%, Basal 42.9%, Normal 57.1%, p=0.006). Among 45 HER2-e patients with a first distant relapse, 25.6% were diagnosed with a brain metastasis and 15.6% had brain-only disease. Conclusions: Molecular subtypes influence the metastatic behaviour of clinically HER2-positive breast cancer. These results, if further validated, may have implication in planning personalized monitoring strategies. Table 1. 5-yr and 10-yr cumulative incidence rates of distant metastasis at specific sites (as first event) according to intrinsic subtype. Citation Format: Maria Vittoria Dieci, Giancarlo Bisagni, Stefania Bartolini, Antonio Frassoldati, Daniele Giulio Generali, Federico Piacentini, Gaia Griguolo, Enrico Tagliafico, Fara Brasó-Maristany, Nuria Chic, Francesca Porra, Roberto Vicini, Roberto D’Amico, Sara Balduzzi, Aleix Prat, PierFranco Conte, Valentina Guarneri. Pattern of distant relapse according to intrinsic molecular subtype in patients with HER2-positive breast cancer: a combined analysis of ShortHER, CherLOB, and two institutional cohorts. [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-11-12.

Abstract P6-01-42: BASELINE 18FDG-PET METABOLIC TUMOUR VOLUME (MTV) AS A POTENTIAL PREDICTIVE FACTOR OF RESPONSE TO METRONOMIC CHEMOTHERAPY (mCHT) IN HR+/HER2- METASTATIC BREAST CANCER (MBC) PATIENTS (pts). PRELIMINARY RESULTS OF THE METRO-PET STUDY

Abstract Background: MBC is an incurable disease and chemotherapy (CHT) represents one option of treatment upfront, in TNBC pts, or at failure of an endocrine therapy + targeted agents in HR+ ones. mCHT was extensively studied in different types of ABC pts and is largely used in clinical practice. 18FDG-PET is often used as a tool for disease staging at baseline and for disease restaging during treatment. Different quantitative and semi-quantitative 18FDG-PET parameters have been investigated as predictive and prognostic biomarkers in NSCLC and other tumours. Aim of the present study is to evaluate the role of baseline SUVmax , global SUVmean, SUVpeak, Metabolic Tumour Volume (MTV) and Total Lesion Glycolysis (TLG) as predictive factors of response to mCHT. Patients and Methods: We identified 36 MBC pts treated with mCHT between 2014 and 2021, with at least two separate 18FDG-PET evaluations. Patients and biological tumour characteristics, previous treatments, site of relapse as well as quantitative pre-treatment 18FDG-PET parameters have been collected. Tumour response was assessed using PERCIST Criteria. Median and mean ± SD 18FDG-PET parameters have been reported according to the type of response. Complete and Partial responses have been grouped together with Stable Disease. Results: Median age was 69 (33-82). Luminal pts were 25 (67.6%), TNBC pts were 16.2%); most were heavily pre-treated for their metastatic disease (≥ 3 lines: 14, 37.8%) and presented ≥ 3 metastatic sites (14, 37.8%). All pts received mCHT, 26 (70.3%) as combination therapy (VRL+CAPE or VRL+CAPE+CTX), or single agent (VRL, 11). Bone was the commonest metastatic site (62.2%). ORR was 43.2%; 7 pts had SD (18.9%), the remaining developed PD (37.8%). Similar values have been observed between the 2 groups in terms of SUVmax , global SUVmean and SUVpeak,. Mean MTV was higher in responder (n=22) vs non responder (n=14) pts, as TLG. Details are reported in Table 1. Conclusions: High mean baseline MTV and TLG seem to be related to response to mCHT in MBC pts. Our observation is in contrast to what is described for other cancer types, especially NSCLC, and for standard neoadjuvant treatment of BC. Considering the peculiar mechanisms of action of mCHT, our preliminary findings warrant further exploration in a larger series of BC pts. Table 1 Baseline 18FDG-PET uptake values in responder and non responder patients Citation Format: Marco Meazza Prina, Irene Gotuzzo, Marina Elena Cazzaniga, Elisabetta De Bernardi, Pietro Cafaro, Serena Capici, Viola Cogliati, Francesca Fulvia Pepe, Federica Cicchiello, Francesca Riva, Nicoletta Cordani, Maria Grazia Cerrito, Elia Anna Turolla, Claudio Landoni, Federica Elisei, Cinzia Crivellaro, Leonardo Virdone, Lavinia Monaco, Alessandro Guidi, Luca Guerra. BASELINE 18FDG-PET METABOLIC TUMOUR VOLUME (MTV) AS A POTENTIAL PREDICTIVE FACTOR OF RESPONSE TO METRONOMIC CHEMOTHERAPY (mCHT) IN HR+/HER2- METASTATIC BREAST CANCER (MBC) PATIENTS (pts). PRELIMINARY RESULTS OF THE METRO-PET STUDY [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-01-42.