Complete Molecular Response Research Articles

Exploring early kinetic profiles of CEA, ctDNA and cfDNA in patients with RAS-/BRAF-mutated metastatic colorectal cancer

IntroductionPatients with metastatic colorectal cancer (mCRC) respond differently to first-line chemotherapy. Early identification of patients with limited or no clinical benefit could prompt a timelier introduction of second-line therapy and potentially lead to improved overall outcomes. Carcinoembryonic antigen (CEA) is currently the only blood-based marker in clinical use for disease control monitoring in mCRC. Circulating cell-free DNA (cfDNA), including circulating tumor DNA (ctDNA) could become a useful surrogate for oncological outcomes. Materials and methodsForty patients with RAS-/BRAF-mutated mCRC from the prospective NORDIC-VII trial (NCT00145314) were included. An exploratory model system was made to describe the early on-treatment kinetics of CEA, cfDNA and ctDNA during first-line oxaliplatin-based chemotherapy, and investigate the associations with radiological response, progression-free survival (PFS) and overall survival (OS). ResultsSummary metrics were made, representing percentage change from treatment start to time-grid day 7 (P7), day 14 (P14), and day 49 (P49); slope from time-grid day 0 to 7 (S7), day 8 to 14 (S14), and day 15 to 49 (S49); and area under the curve from time-grid day 0 to 49 (AUC). Notably P49 and S49 for ctDNA and CEA were associated with radiological response and/or PFS. The early dynamics of the two markers differed substantially, with faster and more marked changes in ctDNA compared with CEA. Nine patients did not reach complete/near complete molecular ctDNA response close to first evaluation (∼week 8), a state associated with a short PFS (HR 2.72; 95% CI 1.22 – 6.06; P = 0.01) and OS (HR 3.12; 95% CI 1.35 – 7.23; P < 0.01). Contrary, twenty-two patients did not reach radiological response (i.e., complete or partial response) at first evaluation, but this was not associated with PFS (HR 1.21; 95% CI 0.64 – 2.30; P = 0.55) nor OS (HR 1.37; 95% CI 0.70 – 2.68; P = 0.37). ConclusionEarly dynamics of ctDNA during first-line oxaliplatin-based chemotherapy hold prognostic value, supporting the idea of prospectively validating a ctDNA-RECIST framework in the early care pathway of mCRC patients. Micro AbstractMetastatic colorectal cancer (mCRC) patients respond differently to chemotherapy, and early identification of patients with limited or no clinical benefit could prompt treatment switching with improved outcomes. We examined CEA and circulating tumor DNA (ctDNA) dynamics during first-line oxaliplatin-based chemotherapy, and their association with radiological response/survival (N=40). ctDNA dynamics hold prognostic value, supporting the idea of prospectively validating a ctDNA-response framework early in the care pathway.

Voxel-Based Dosimetry Predicts Local Tumor Progression Post 90Y Radiation Segmentectomy of Colorectal Liver Metastases

Background Radiation segmentectomy (RS) is an alternative potential local curative treatment for selected colorectal liver metastases (CLMs) not amenable to ablation or limited resection. Purpose The aim of this study was to evaluate the dosimetric response of low volume CLMs to RS in heavily pretreated patients who are not candidates for resection or percutaneous ablation. Patients and Methods This single-center retrospective study evaluated CLMs patients treated with RS (prescribed tumor dose &gt;190 Gy) from 2015 to 2023. RS doses to tumor(s) and margins were calculated from SPECT/CT and PET/CT images. Response and local tumor progression (LTP) were assessed using anatomic (RECIST 1.1) and metabolic (PERCIST) criteria. LTP-free survival (LTPFS) and overall survival were estimated with Kaplan-Meier methodology. Variables were assessed as predictors of LTPFS using the Cox proportional hazards model. Results Thirty-six patients underwent 38 RS procedures to treat 57 tumors. Median time from initial diagnosis to detection of liver metastases and RS were 16.4 (interquartile range: 6.5–32.2) and 26.8 (interquartile range: 12.5–40.0) months, respectively. Median overall survival after RS was 14.3 (95% confidence interval [CI]: 10.8–30.7) months. Predictors of LTPFS included tumor number(s), mean tumor dose (MTD), and margin mean absorbed dose (MMAD). Complete radiographic (hazards ratio [HR]: 1.29e-16, 95% CI: 4.06e–17-4.07e-16, P &lt; 0.001) and metabolic response (HR: 0.38, 95% CI: 0.15–0.95, P = 0.038) correlated with prolonged LTPFS. One-year LTPFS rate was 83.3% for tumors receiving MTD ≥400 Gy and a 5-mm surrounding MMAD ≥350 Gy (P = 0.006). No instances of LTP were observed when tumors received stereotactic irradiation over 300 Gy (at least 95% of the tumor volume received ≥300 Gy). One-year LTPFS rate for tumors receiving MTD ≥400 Gy was 68.6% versus 14.3% for those that did not reach this threshold (P = 0.013). In multivariate analysis, MTD ≥400 Gy and 5-mm MMAD ≥350 Gy were independent predictors of LTPFS (HR: 0.11; 95% CI: 0.01–0.81; P = 0.03). Conclusions MTD ≥400 Gy, MMAD ≥350 Gy, and stereotactic tumor irradiation ≥300 Gy are associated with prolonged LTPFS after RS for CLMs.

TRBC1-CAR T cell therapy in peripheral T cell lymphoma: a phase 1/2 trial.

Relapsed/refractory peripheral T cell lymphomas (PTCLs) are aggressive tumors with a poor prognosis. Unlike B cell lymphomas, treatment of PTCL has not benefited from advances in immunotherapy. This is largely due to a lack of suitable target antigens that discriminate malignant from normal T cells, thus avoiding severe immunosuppression consequent to depletion of the entire T cell compartment. We recently described a targeting strategy based on the mutually exclusive expression of T cell antigen receptor beta-chain constant domain (TRBC) 1 and 2. Selective targeting of the T cell antigen receptor beta-chain expressed by the (clonal) malignancy spares normal T cells expressing the other chain. The LibraT1 study is an ongoing, multicenter, international, single-arm phase 1/2 study of TRBC1-directed autologous chimeric antigen receptor (CAR) T cells (AUTO4) in relapsed/refractory TRBC1-positive PTCL. Primary objectives were assessment of safety and tolerability of AUTO4 infusion. Key secondary endpoints included efficacy, CAR T cell expansion and persistence. Here we describe the findings from dose escalation in LibraT1 in the first ten patients, in a non-prespecified interim analysis. AUTO4 resulted in low frequency of severe immunotoxicity, with one of ten patients developing grade 3 cytokine release syndrome. Complete metabolic response was observed in four of ten evaluable patients, with remissions being durable beyond 1 year in two patients. While an absence of circulating CAR T cells was observed, CAR T cells were readily detected in lymph node biopsy samples from sites of original disease suggesting homing to tumor sites. These results support the continuing exploration of TRBC1 targeting in PTCL. ClinicalTrials.gov registration: NCT03590574 .

Predictors for Disease-Free and Progression-Free Survivals in Metabolic Responders and Non-Responder on Follow-Up 18FDG PET/CT after Chemoradiation in Patients With Nasopharyngeal Cancer.

To determine disease free survival (DFS) and progression free survival (PFS) and their predictors in patients with nasopharyngeal cancer (NPC) having achieved complete (CMR) and partial metabolic response (PMR) on post-chemoradiation (CRT) 18FDG PET/CT. Retro-prospective study conducted at PET/CT Section of JCIA accredited healthcare facility of Pakistan. Total 73 patients of NPC patients who had baseline and post-CRT 18FDG PET/CT were included and prospectively followed till predefined study end points of recurrence or disease progression or death from April-2016 till January 2024. Based on CMR on post-CRT 18FDG PET/CT, 45 patients labelled as responders while 28 with PMR as non-responders. Using logistic regression and ROC analysis, the predictors of recurrence and disease progression were analyzed in both groups. Kaplan Meier's survival plots were analyzed to measure DFS in responders and PFS in non-responders respectively. Body mass index (BMI), SUVmax and Stage-IV disease were found significantly higher in non-responder group. DFS in responders was significantly higher than PFS in non-responder (60.157 month ± 8.047 Vs 8.145 months ± 1.851). DFS was seen in 84% of responder group with 16% recurrence (7/45). Baseline SUVmax >14.2 and primary tumor size (PTS) > 41 mm were found significant predictors of recurrence in responder group. In the non-responder group, the PFS was found in 54% patients while 46% patients (n=13/28; 2 expired) had disease progression. No significant predictor was found for PFS in the non-responder group. In DFS the mean survival was significantly higher in patients with SUVmax ≤14.2 versus >14.2 (Mean Survival 67.390 vs. 38.283 months; Logrank 9.899; p=0.0017*). However, near significant difference was observed in non-responder group in their PFS at SUVmax ≤11.9 vs. >11.9 (Mean Survival 10.00 vs. 7.05 months; Logrank=3.096; p=0.0798). 18FDG PET/CT scan precisely stratifies the treated NPC patients into responders having longer DFS and non-responders having shorter PFS. Higher BMI, SUVmax of primary tumor and metastatic disease were found to have significant association in non-responders. In responders, PTS >41 mm and its SUVmax >14.2 were found significant predictors of recurrence. In non-responders, SUVmax >11.9 was found to have near significant association with disease progression.

Multicenter randomized phase III study of high-dose therapy with autologous stem cell transplantation versus observation for patients with newly diagnosed peripheral T-cell lymphoma who achieved complete metabolic response after induction therapy (JCOG2210, TRANSFER study).

Patients with peripheral T-cell lymphoma demonstrated a poor prognosis after obtaining a complete response with induction treatment compared to those with B-cell lymphoma. Once it relapsed, curative treatment is frequently limited to invasive treatments with significant treatment-related mortality, including allogeneic stem cell transplantation. The limitations of these treatment choices indicate the necessity for developing optimal consolidation therapies to prevent relapse. This multicenter randomized phase III trial aims to confirm the superiority of the high-dose therapy with autologous stem cell transplantation over observation alone in terms of progression-free survival for patients with newly diagnosed peripheral T-cell lymphoma who achieved complete metabolic response after induction therapy. A total of 140 patients from 52 hospitals will be enrolled in Japan over 5.5years. This trial is registered in the Japan Registry of Clinical Trials as jRCTs031240169 (https://jrct.niph.go.jp/latest-detail/jRCTs031240169).

A Rare Case of Acute Promyelocytic Leukemia with Concomitant PML-RARA Fusion and TP53 Loss/ider(17)(q10)t(15;17) Showing Complete Clinical and Molecular response: A Case Report

Abstract Introduction/Objective To report a case with rare cytogenetic abnormality: a patient with newly diagnosed acute promyelocytic leukemia (APL) with cytogenetic findings of t(15;17)(q24;q21), trisomy 8 and ider(17)(q10)t(15;17)-TP53 loss. The presence of isochromosome 17q may indicate the possibility of an unfavorable outcome. However, the case showed complete clinical and molecular response. Methods/Case Report A case of a 53-year-old female with history of ITP post-splenectomy presented with persistent hematuria, easy bruising, and worsening fatigue. She had mild microcytic anemia, moderate thrombocytopenia, 3% promyelocytes, and 14% blasts on differential CBC count. With increased PT, PTT, LDH, Uric acid and decreased fibrinogen level, APL was clinically suspected. The patient was initiated on all-trans retinoic acid (ATRA), allopurinol, and IV fluids. Bone marrow (BM) biopsy confirmed the diagnosis with unusual cytogenetic findings. The patient underwent induction and consolidation therapies (4 weeks each) with ATRA plus Arsenic Trioxide (ATO) and followed- up with a series of marrow biopsies, cytogenetic and molecular studies. Results (if a Case Study enter NA) The patient demonstrated complete clinical, histological, and molecular response. She tolerated the treatment without major side effects, showing improvement in CBC counts, coagulation profile and tumor lysis labs. Initial BM exam revealed hypercellularity with infiltrating sheets of atypical hypergranular promyelocytes (~80%) and minimal residual left trilineage hematopoiesis. Flow cytometry revealed a CD34 negative, CD117 variable abnormal promyelocyte population (~67% of total events). FISH was positive for PML/RARA translocation (15; 17) and TP53 loss. Karyotype showed 46,XX,der(15)t(15;17)(q24;q21),ider(17)(q10)t(15;17)[12]/47,idem,+8[9]. By the end of treatment, BM biopsy was normocellular with trilineage hematopoiesis and no definitive evidence of acute leukemia or increase in blasts. The Karyotype was normal. Quantitative PCR for PML-RARA was negative, indicating complete molecular remission. Conclusion In this unique case of APL with unusual cytogenetic abnormalities the literature demonstrates controversial data. The patient achieved complete clinical and molecular remission following standard treatment. This may indicate the limited prognostic significance of these additional cytogenetic abnormalities in this case.

Diffuse Large B-cell Lymphoma (DLBCL) involving the Uterine Corpus presenting with Abnormal Uterine Bleeding: A Rare Case Report

Abstract Introduction/Objective Diffuse Large B-cell Lymphoma (DLBCL) is an aggressive type of non-Hodgkin lymphoma. Lymphomas affecting the female genital system are extremely rare, accounting for about 1% of extra-nodal lymphomas, with DLBCL being the most common type. We present a rare case of uterine lymphoma presenting with abnormal uterine bleeding. Methods/Case Report A 50-year-old female presented with abnormal uterine bleeding and fatigue for the past three weeks. Laboratory work-up showed hemoglobin level of 5.5 g/dL. Pelvic ultrasound revealed thickening of the endometrium and a 1.6 cm hypoechoic uterine lesion along with multiple enlarged bilateral adnexal lymph nodes. Histological examination of the endometrial biopsy demonstrated endometrial fragments with diffuse subepithelial proliferation of large, poorly differentiated cells with round nuclear contours, finely dispersed chromatin, relatively inconspicuous nucleoli and moderate amount of cytoplasm. Many scattered mitoses and apoptotic bodies were present. Primary set of immunohistochemical stains were performed to rule out primary uterine epithelial or mesenchymal tumors. The tumor cells were negative for pan-keratin, high and low molecular weight keratins and positive for CD45. Further work-up demonstrated CD20 positivity. It was diagnosed as DLBCL with a non-germinal center, double expressor phenotype and a high Ki-67 proliferation. Fluorescence in-situ hybridization studies were negative for MYC and BCL6 gene rearrangements and IGH-BCL2 translocation. Further radiological workup revealed diffuse lymphadenopathy with multiple pulmonary and renal nodules consistent with Stage IV DLBCL. She was treated with six cycles of R-CHOP regimen, and complete metabolic response was achieved. Results (if a Case Study enter NA) NA Conclusion Uterine lymphomas are very rare and on small biopsies may histologically mimic poorly differentiated uterine malignancies such as dedifferentiated/undifferentiated carcinomas. Adding lymphoma lineage markers to poorly differentiated tumors is recommended to avoid missing such a rare entity.

Different prognosis according to treatment in patients with acute promyelocytic leukemia: How the outcome changed over time.

A comprehensive analysis of 220 patients diagnosed with APL between 1993 and 2022 is here reported. Overall, 214 patients (97.2%) received induction therapy. Complete response (CR) was achieved in 97.4%, 100%, 100%, and 27% of patients treated with AIDA protocol, AIDA + Ara-C, ATRA + ATO, and ATRA monotherapy, respectively. Molecular complete response (CRMRD-) was achieved in 96.8% cases, and 142 patients proceeded to maintenance therapy. Overall, the 3-year and 5-year overall survival (OS) rates were 80.8% (95% CI, 78.1-83.5) and 79.1% (95% CI, 76.4-81.8), respectively. Considering only patients who completed induction and maintenance therapy, the 5-year OS rates were 82.1% (95% CI, 77.5-86.7) for the AIDA0493 cohort, 87.5% (95% CI, 84.4-91.1) for the AIDA2000 cohort, and 100% for the APL0406 cohort (p = 0.044). Additionally, the disease-free survival (DFS) rates were 65.7% (95% CI, 60.4-70.9), 70% (95% CI, 65.8-75.2), and 95.1% (95% CI, 91.7-98.5) (p = 0.016), respectively. Among low and intermediate-risk patients, age > 70 years (p = 0.027) and relapse (p < 0.001) were significantly associated with reduced outcomes. This study contributes to the advancement of our understanding of APL treatment, underscoring the ongoing need for research to enhance outcomes and explore new therapeutic approaches and prognostic factors.

Olverembatinib treatment in adult patients with newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia.

Olverembatinib is a novel orally administered third-generation tyrosine kinase inhibitor (TKI) with definitive responses in T315I-mutant chronic myeloid leukemia (CML) patients. However, its value in newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL) remained unclarified. In this multiple-center study, 20 patients with de novo Ph + ALL were treated with olverembatinib-based regimens as frontline therapy. All patients acquired complete remission (CR) after induction. 85% of patients achieved complete molecular response (CMR) within three months, contributed mainly by the addition of blinatumomab. A total of 45% of patients experienced mild hematological treatment-related adverse events (TRAEs). Olverembatinib-based treatment led to promising outcomes in de novo Ph + ALL patients but warranted further studies to investigate the best-combined strategy.

The value of semiquantitative PET features and end-of-therapy PET in grade 3B follicular lymphoma.

Grade 3B follicular lymphoma (G3BFL) is a rare lymphoma thought to sit on a continuum between low-grade FL and diffuse large B-cell lymphoma (DLBCL). The prognostic impact of quantitative positron emission tomography (PET) metrics such as total metabolic tumour volume (TMTV), total lesion glycolysis (TLG), and maximum standard uptake value (SUVmax) have been extensively analysed in FL and DLBCL, but G3BFL data are lacking. Here, we describe PET outcomes and radiomic characteristics in 46 G3BFL cases uniformly treated with R-CHOP (like) chemotherapy. Central semi-automated PET TMTV, TLG, and SUVmax analyses, using MIM software, were correlated with clinical outcomes and compared with published results in low-grade FL and DLBCL. In G3BFL, the end-of-treatment complete metabolic response was associated with improved progression-free survival (PFS; p = 0.002) and overall survival (OS; p = 0.04). G3BFL median TLG (1455) and SUVmax (16.50) sit between published values for low-grade FL (TLG: 1112, SUVmax: 11.3) and DLBCL (TLG: 3004, SUVmax: 24.35). No association between TMTV (>350 cm3) and survival was seen (PFS: p = 0.24; OS: p = 0.40). High SUVmax (>19.2) and TLG (>2760) both conferred inferior PFS but not OS (PFS: SUVmax p = 0.004; TLG p = 0.05). These data support the routine incorporation of PET radiomics at baseline and treatment response for G3BFL.

6850 A Case of Anaplastic Thyroid Carcinoma With a Complete Metabolic Response to Pembrolizumab

Abstract Disclosure: E. Tirthani: None. J.T. Kung: None. Background: Anaplastic thyroid carcinoma (ATC) is an aggressive disease with limited therapeutic options and generally poor prognosis. Post-surgery, most patients are treated with a combination of chemotherapy, radiation, and tyrosine kinase inhibitors +/- immune checkpoint inhibitors. We describe a unique case of ATC with a complete metabolic response to pembrolizumab, a selective PD-1 inhibitor, as evidenced by imaging. Clinical Case: A 69-year-old female presented to the clinic for evaluation of a rapidly enlarging neck mass. The initial ultrasound showed a large mixed cystic-solid right thyroid nodule with irregular margins with micro- and macrocalcifications, which was biopsied. Cytology showed discohesive high-grade malignant tumor cells with enlarged nuclei, nuclear hyperchromasia in the background of necrosis, and dense neutrophilic infiltration concerning for ATC. A CT scan of the neck and chest showed a complex cystic thyroid mass with central necrosis and calcification with paratracheal, supraclavicular, and mediastinal lymphadenopathy. MRI of the brain was negative for metastatic disease. The patient underwent a total thyroidectomy with right and left level 6 and 7 neck dissection. Intra-operatively, gross extrathyroidal extension of the tumor was noted to the right carotid, larynx, right recurrent laryngeal nerve, and esophagus, with residual tumor left behind near the larynx. Pathology confirmed stage IVC ATC, positive for PIK3CA, NF1, p53 mutations, and BRAF negative. 90% of tumor cells showed PD-L1 expression on immunohistochemical staining. The post-surgical PET scan showed two discrete, well-defined foci of very intense FDG uptake, corresponding to the right lower cervical and para-esophageal lymph nodes with no evidence of distant metastasis. Systemic chemotherapy with carboplatin and paclitaxel (5 cycles) was initiated with concurrent intensity modulated radiation therapy (total 60 Gy/40 fractions to thyroid bed and bilateral neck). Repeat imaging showed minimal change in the size of the PET-positive lymph nodes. Immunotherapy was initiated and with just 2 cycles of 400 mg IV pembrolizumab, a repeat PET scan was obtained, which showed a complete metabolic response to therapy. Minimal residual FDG activity in the right supraclavicular region was thought to be secondary to posttreatment changes. The patient was able to resume her activities of daily living and had an improvement in appetite. The plan is to continue 400 mg IV pembrolizumab every 6 weeks while cautiously assessing for adverse effects from immunotherapy. Conclusion: It is rare to see a complete metabolic response to therapy with pembrolizumab without concurrent use of tyrosine kinase inhibitors in patients with ATC. A high tumoral PD-L1 expression may be the key to having this kind of dramatic response. Presentation: 6/3/2024

Peptide receptor radionuclide therapy for ectopic Cushing's syndrome caused by metastatic neuroendocrine neoplasms.

Metastatic gastroenteropancreatic neuroendocrine neoplasms (GEPNEN) can cause ectopic Cushing's syndrome (ECS). ECS is highly morbid and medical therapy is complex and can be ineffective. Patients unsuitable for bilateral adrenalectomy (BA) have dismal outcomes. Peptide receptor radionuclide therapy (PRRT) is a rational option for hormone and disease control in ECS caused by NEN with high somatostatin receptor (SSTR) expression. To describe the characteristics and outcomes of patients with ECS treated with PRRT. Single-centre, retrospective analysis of imaging, biochemistry and outcomes of seven consecutive patients with ECS caused by metastatic GEPNEN treated with PRRT from 2006 to 2023. Patients were aged 17-75 (female n = 6). The primary site was the pancreas (5/7) and rectum (2/7). Six patients were on medical therapy for ECS at baseline (one had a previous BA). A median of 34.4 GBq of [177Lu]Lu-DOTA-octreotate was given. [90Y]Y-DOTA-octreotate (one patient) and [111In]In-octreotide (one patient) were also used. Five patients had radiosensitising chemotherapy. Five patients had a flare of ECS within 1 week of PRRT cycle 1 (PRRT-C1). Following PRRT-C1, 5/7 patients had complete biochemical resolution of ECS at 1.5-6 months (four ongoing; one recurred after 12 months and had elective BA at 18 months). Best metabolic response on [18F]F-FDG PET/CT: Four patients had a complete metabolic response (CMR), and one had a partial metabolic response. PFS was 3-208 months. Two patients progressed at the first follow-up. The longest ECS remission and CMR continues at >17 years. PRRT can be effective for ECS caused by metastatic SSTR-positive GEPNEN and should be considered in its treatment algorithm.

New ABL1 Kinase Domain Mutations in BCR::ABL1-Positive Acute Lymphoblastic Leukemia.

Since the development of the first-generation Tyrosine Kinase Inhibitor (TKI), it has played a crucial role in the treatment of BCR::ABL1-positive acute lymphoblastic leukemia (ALL) and chronic myeloid leukemia (CML). However, ABL1 kinase domain (ABL1 KD) mutations confer resistance to several TKIs. These mutations have been extensively studied in chronic myeloid leukemia (CML) but less so in BCR::ABL1-positive acute lymphoblastic leukemia (ALL). Our study aimed to analyze the the ABL1 KD mutations in 97 consecutive newly-diagnosed adults with BCR::ABL1-positive ALL before therapy, in cytogenetic complete remission and at relapse with next generation sequencing (NGS). The relationship between ABL1 KD mutations and TKI selection was also analyzed. Previously unreported ABL1 KD mutations R239G, F401V/L, R516L and K262T were the most prevalent in pre-therapy and cytogenetic remission samples, whereas T315I/P and P-loop mutations were most prevalent in relapse samples. R239G, F401V/L, R516L and K262T are related to the BCR::ABL1 structure, whereas T315I/P and P-loop mutations directly alter kinase activity. BaF3 cells transfected with ABL1 KD F401V, K262T, R239G, or R516L mutations were resistant to imatinib but strongly inhibited by olverembatinib with IC50 values of 0.73 to 1.52nM. Meanwhile, olverembatinib had advantages in increasing complete molecular response (CMR) and good prognosis. Overall, our findings indicate the prevalence and impact of new ABL1 KD mutations in BCR::ABL1-positive ALL patients, highlighting the necessity for effective therapies targetingthese mutations.

Immunotherapy response and resistance in patients with advanced uveal melanoma: a retrospective cohort study

Metastatic uveal melanoma (mUM) is associated with poor prognosis. Ipilimumab/nivolumab has shown antitumor efficacy in phase II studies. Tebentafusp resulted in longer overall survival (OS) compared to investigator`s choice in a phase III study. We sought to describe the radiological response patterns of mUM patients treated with immunotherapy. Patients with mUM treated with ipilimumab/nivolumab and tebentafusp between July 2018 and December 2022, with available radiological assessment per RECISTv1.1 and/or imPERCIST5, were retrospectively identified and included. Progression-free survival (PFS) and OS rates, liver-specific response and pathological assessment in available liver biopsies were evaluated. In the ipilimumab/nivolumab group, median PFS (mPFS) was 2.9 months (95% CI 2.2–28.6) and mOS 28.9 months (95% CI 12.7-NR). Complete (CMR) and partial (PMR) metabolic response per imPERCIST5, and partial response (PR) per RECISTv1.1 were associated with longer PFS and OS by trend, compared to morphologically and metabolically stable or progressive disease. In the tebentafusp group, mPFS was 2.7 months (95% CI 2.2–3) and mOS 18.6 months (95% CI 11.5-NR). PMR and PR were associated with longer PFS by trend. In both treatments, the overall treatment response was associated with the radiological response at the liver site. In available liver tumor biopsies, differences in pathological and radiological responses were noted. ImPERCIST5 and RECIST v1.1 are valuable tools in the radiological response assessment, but both methods display limitations. Accurate biomarkers to stratify patients at risk for disease progression and future translational studies to investigate mechanisms of response and resistance are required.

Neoadjuvant Immunotherapy and De-Escalation of Surgery in Locally Advanced Breast Implant-Associated Anaplastic Large Cell Lymphoma (BIA-ALCL)

Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a rare form of non-Hodgkin T cell lymphoma diagnosed in patients with a history of breast implants. Most patients develop a periprosthetic effusion at early stages of disease while less common presentations include a palpable mass, severe capsular contracture, lymphadenopathy, or cutaneous erythema. Due to the complex nature of this disease, a multidisciplinary approach is necessary for optimal management, particularly in locally advanced disease or inoperable patients. We present the successful use of neoadjuvant therapeutic protocols in two cases of locally advanced BIA-ALCL. The first case, a 52-year-old patient with a left breast mass-like stage III disease who underwent combined targeted immunotherapy and chemotherapy (BV-CHP). Following a complete radiological and metabolic response, the patient underwent bilateral implant removal, right total intact capsulectomy, left en bloc capsulectomy and skin resection from the left inframammary fold in continuity with the capsule. The second case, a 65-year-old patient with a right breast swelling and mass-like stage IIA disease who received targeted immunotherapy, Brentuximab vedotin (BV). Following a complete metabolic response, she underwent bilateral implant removal and en bloc capsulectomy. A literature review and the reported cases suggest the effectiveness of targeted immunotherapy as monotherapy or in combination with chemotherapy in locally advanced BIA-ALCL in disease downstaging, surgical de-escalation, reduction of significant post-operative complications and an acceptable tolerance profile. Although surgery is an essential part of treatment, timing and type of intervention should be carefully planned, especially when primary, radical resection is uncertain.

Mantle cell lymphoma with skin involvement: Case report of a rare manifestation in a patient with initial diagnosis of chronic lymphocytic leukemia

Mantle cell lymphoma is a rare subtype of B-cell non-Hodgkin's lymphoma, which mainly affects males. It has a variable clinical presentation, with a course ranging from indolent cases that do not require treatment for years to very aggressive cases. Skin involvement is a rare event. Although most patients have disease in stage III or IV at diagnosis, they generally present with good functional status. In immunohistochemistry, CD5 is commonly expressed, a feature it shares with chronic lymphocytic leukemia. Cyclin D1 and SOX11 expression are present in almost all cases. Treatment depends on multiple factors such as age, frailty, comorbidities, disease stage, symptoms and morphological characteristics. We present the case of a male patient initially diagnosed with chronic lymphocytic leukemia who was started on treatment with ibrutinib. A biopsy of the right earlobe was subsequently performed, which documented secondary skin involvement due to a classic histological variant of mantle cell lymphoma. The patient was treated with chemotherapy between March and July 2022, with positron emission tomography at the end of the proposed cycles with complete metabolic response, so maintenance treatment with rituximab was performed and subsequently consolidated with an autologous bone marrow transplant. To date, the patient is in remission of the disease.

Effective Treatment of Primary Orbital Squamous Cell Carcinoma with Radiotherapy: A Rare Case Report and Literature Review Update

AbstractPrimary squamous cell carcinoma (SCC) of the orbit is exceptionally rare, comprising only a small fraction of ocular tumours, with most cases being secondary to tumours originating from nearby structures or due to distant metastasis. We present a case of primary orbital SCC in a 60-year-old male, discussing its diagnostic workup, imaging findings, and multidisciplinary management. The patient underwent definitive radiotherapy with concurrent chemotherapy after being deemed inoperable. Without any severe treatment-related adverse event, the patient achieved a complete metabolic response at 7 months post-treatment with maintained vision. As evident from a review of the literature, treatment approaches vary widely in this group of patients, with radiotherapy emerging as a successful modality in achieving disease control while preserving vision with acceptable toxicity. This case underscores the complexity of managing primary orbital SCCs and highlights the efficacy of radiotherapy in achieving favourable outcomes.

Metabolic Imaging of Advanced Basal Cell Carcinoma Treated with Sonidegib: A Retrospective Case Series Study.

Background: Positron emission tomography/computed tomography (PET/CT) with 18F-fluorodeoxyglucose (18F-FDG) is a firmly established tool in oncology and is gaining importance in dermato-oncology. However, its use in advanced basal cell carcinoma (BCC) is limited, with only a few case reports and a single study focused on vismodegib. This study evaluates the role of 18F-FDG PET/CT in advanced BCC treated with sonidegib. Methods: We retrospectively assessed the clinical data of patients with advanced BCC who underwent 18F-FDG PET/CT between January 2022 and January 2024. Inclusion criteria included histologically confirmed BCC, FDG-avid lesions on baseline PET/CT, and a minimum follow-up of 6 months. Metabolic response was assessed using the PET Response Criteria in Solid Tumors (PERCIST). Results: Four patients with advanced BCC treated with sonidegib were included, presenting with a total of 10 hypermetabolic lesions at baseline PET/CT. The mean interval between baseline and follow-up scans was 8.7 ± 1.6 months. According to PERCIST, two patients achieved a complete metabolic response (CMR), while the other two had stable metabolic disease (SMD). Low baseline-standardized uptake values (i.e., SUVmax, SUVmean) and reduced total lesion glycolysis (TLG) were associated with CMR. No relapses were observed during follow-up. Conclusions: This study suggests that 18F-FDG PET/CT may help identify advanced BCC patients who are likely to benefit from sonidegib treatment. Further research is needed to fully explore the potential of PET/CT in this specific clinical context.

Omission of Radiotherapy in Primary Mediastinal B-Cell Lymphoma: IELSG37 Trial Results.

The role of consolidation radiotherapy in primary mediastinal B-cell lymphoma (PMBCL) patients is controversial. The IELSG37 trial, a randomized non-inferiority study, aimed to assess whether irradiation can be omitted in PMBCL patients with complete metabolic response (CMR) after induction immunochemotherapy. Primary endpoint was progression-free survival (PFS) at 30 months post-randomization. Patients with CMR were randomly assigned to observation or consolidation radiotherapy (30 Gy). With a non-inferiority margin of 10% (assuming a 30-month PFS of 85% in both arms), a sample size of 540 patients was planned with 376 expected to be randomized. The observed events were considerably lower than expected, therefore, primary endpoint analysis was conducted when ≥95% of patients were followed for ≥30 months. Of 545 patients enrolled, 268 were in CMR after induction and were randomized to observation (n=132) or radiotherapy (n=136). The 30-month PFS was 96.2% in the observation arm and 98.5% in the radiotherapy arm, with a stratified hazard ratio of 1.47 (95%CI, 0.34 to 6.28) and absolute risk difference of 0.68% (95%CI, -0.97% to 7.46%). The 5-year overall survival was 99% in both arms.Non-randomized patients were managed according to local policies. Radiotherapy was the only treatment in 86% of those with Deauville score (DS) 4 and in 57% of those with DS 5. The 5-year PFS and OS of patients with DS 4 (95.8% and 97.5%, respectively) were not significantly different from those of randomized patients. Patients with DS5 had significantly poorer 5-year PFS and OS (60.3% and 74.6%, respectively). This study, the largest randomized trial of radiotherapy in PMBCL, demonstrated favorable outcomes in patients achieving CMR with no survival impairment for those omitting irradiation.

Role of serial fluorodeoxyglucose positron emission tomography-computed tomography (18FDG-PET-CT) in assessing treatment response in treatment naïve chronic pulmonary aspergillosis subjects.

The role of 2-deoxy-2-18(F) fluoro-D-glucose (FDG) positron emission tomography (PET)-computed tomography (CT) in assessing treatment response in chronic pulmonary aspergillosis (CPA) remains to be determined. To compare changes in FDG-PET/CT parameters in CPA subjects with treatment success or failure. We treated consecutive treatment-naïve CPA subjects with six months of oral itraconazole. We performed PET-CT at baseline and six months. A multi-disciplinary team categorized response as treatment success or failure. We recorded the maximum standardised uptake value (SUVmax), SUVpeak, and total glycolytic activity (TLG). After treatment, FDG uptake similar to the background uptake or ≥13 units decline in Z-score was considered a complete metabolic response (CMR). A >25%, >30%, and > 45% decline in SUVmax, SUVpeak, and TLG was labelled as a partial metabolic response (PMR). A >30%, >30%, or >75% increase in the SUVmax, SUVpeak, and TLG represented progressive metabolic disease. We included 94 CPA subjects (63 males) with a mean age of 46.2 years. A follow-up PET-CT was performed on 77 subjects. We recorded treatment success and failure in 43 and 34 subjects. The median SUVmax at baseline was 6.7, which significantly reduced with treatment. CMR was seen in 18.6% of those with treatment success and none with treatment failure. A higher proportion of subjects with treatment success achieved PMR. 19% of the subjects with treatment success had progressive metabolic disease. FGD-PET/CT demonstrated metabolic activity in all CPA subjects. Most PET-CT parameters improved with treatment; however, one-fifth of the subjects were misclassified on PET-CT.