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B Introduction: b R-CHOP remains the standard of care in DLBCL yet for up to 40% of patients (pts.) REMODL-A: A RANDOMISED PHASE II EVALUATION OF MOLECULAR GUIDED THERAPY FOR DIFFUSE LARGE B-CELL LYMPHOMA (DLBCL) WITH ACALABRUTINIB - ONGOING TRIAL In the phase Ib/II ACCEPT study (NCT03571308), acalabrutinib (A), a second generation Bruton Tyrosine Kinase inhibitor with enhanced kinase selectivity and a potential for better tolerability, was assessed in combination with R-CHOP in patients with I de novo i DLBCL. [Extracted from the article]

Introduction The incidence of skeletal metastases from hepatocellular carcinoma (HCC) is estimated to be 2–16%. It is well established that radioisotope bone scans can detect cancer earlier than cross sectional imaging. The role of bone scans in pre-transplant assessment has been discussed in the literature but its place in the assessment algorithm is not clearly established. Aim The aim of this study is to determine the utility of radioisotope bone scans in patients with a diagnosis of HCC undergoing transplant pre-assessment. Method Radioisotope bone scan results were reviewed for all patients undergoing liver transplant assessment for HCC at our unit from 1989 to 2009. Patients were initially selected for transplant assessment based on favourable HCC staging on cross sectional imaging. Patients undergoing bone scan had the result reviewed retrospectively as normal or abnormal. All abnormal scans we then reassessed against all available imaging and classified as showing benign or malignant changes. Patient outcomes were considered in relation to bone scan results. Results During this period 216 patients with a primary or secondary diagnosis of HCC were assessed for liver transplantation. Two hundred and three patients were listed for transplant and 148 were eventually transplanted. The results of their bone scans are as below (). Results Amongst patients listed for transplant, 22 (11%) cases had abnormal bone scans with 12 cases in transplanted group showing false positive results for reasons including degenerative changes, healing traumatic fractures and tracer uptake in gynaecomastia. One patient had a scan with high suspicion for bony secondaries. This patient initially listed for transplant was removed from the list due to active substance misuse, and subsequently became too ill before bony abnormalities could be confirmed. The recurrence rates of HCC were 12.5 % in transplanted patients who underwent bone scans and 9% in those transplanted without a bone scan. Conclusion Bone scans were not performed as rigorously as expected with 40% of listed patients with no prior radioisotope imaging. However there were no significant differences in recurrence rates in those that did and did not have bones scans. In a population of patients assessed for liver transplant with cross sectional imaging indicating HCC to be within transplant criteria bone scans had a false positive rate of 18% (24/131). The result of bone scanning did not influence the decision to list with only 1 patient exhibiting feature of bony metastases. This patient was subsequently removed from the list for other reasons. [ABSTRACT FROM PUBLISHER]

Purpose: Preoperative nodal staging is important for planning treatment in cervical cancer and endometrial cancer, but remains challenging. We compare nodal staging accuracy of 18 F-ethyl-choline-(FEC)-PET/CT, 18 F-fluoro-deoxy-glucose-(FDG)-PET/CT, and diffusion-weighted-MRI (DW-MRI) with conventional morphologic MRI., Experimental Design: A prospective, multicenter observational study of diagnostic accuracy for nodal metastases was undertaken in 5 gyne-oncology centers. FEC-PET/CT, FDG-PET/CT, and DW-MRI were compared with nodal size and morphology on MRI. Reference standard was strictly correlated nodal histology. Eligibility included operable cervical cancer stage ≥ 1B1 or endometrial cancer (grade 3 any stage with myometrial invasion or grade 1-2 stage ≥ II)., Results: Among 162 consenting participants, 136 underwent study DW-MRI and FDG-PET/CT and 60 underwent FEC-PET/CT. In 118 patients, 267 nodal regions were strictly correlated at histology (nodal positivity rate, 25%). Sensitivity per patient ( n = 118) for nodal size, morphology, DW-MRI, FDG- and FEC-PET/CT was 40%*, 53%, 53%, 63%*, and 67% for all cases (*, P = 0.016); 10%, 10%, 20%, 30%, and 25% in cervical cancer ( n = 40); 65%, 75%, 70%, 80% and 88% in endometrial cancer ( n = 78). FDG-PET/CT outperformed nodal size ( P = 0.006) and size ratio ( P = 0.04) for per-region sensitivity. False positive rates were all <10%., Conclusions: All imaging techniques had low sensitivity for detection of nodal metastases and cannot replace surgical nodal staging. The performance of FEC-PET/CT was not statistically different from other techniques that are more widely available. FDG-PET/CT had higher sensitivity than size in detecting nodal metastases. False positive rates were low across all methods. The low false positive rate demonstrated by FDG-PET/CT may be helpful in arbitration of challenging surgical planning decisions., (©2021 The Authors; Published by the American Association for Cancer Research.)

Head and neck paragangliomas (HNPGLs) are rare tumours with ~ 30% genetic mutations, mainly in succinate dehydrogenase (SDHx) genes. The utility of FDG PET-CT in HNPGLs is questioned by recent developments in novel radiotracers. We therefore performed a retrospective study in a single tertiary referral centre to address the utility of FDG PET/CT in HNPGLs., Methods: Clinical data on genetic testing and follow-up were collected for patients who had FDG PET-CT scans from 2004 to 2016. Receiver operator characteristic (ROC) analysis was used to compare standardized uptake values (SUVs), metabolic tumour volume (MTV) and total lesion glycolysis (TLG) between lesions in patients who had a clinically related event: event (+) and those who did not: event (-). Similarly, we compared PET parameters between SDHx+ patients and a control group with low probability of mutation., Results: Of 153 HNPGL patients, 73 (29 SDHx+) with 93 FDG-positive lesions were identified: 53.8% of lesions were assessed in a pre-therapeutic setting. In comparison with a reference extracted from clinicoradiological database, FDG PET-CT showed good performance to detect HNPGLs (96.6% accuracy). In this study population, 16 disease progression, 1 recurrence and 1 death were recorded and event (+) patients had lesions with higher SUVmax (p = .03 and p = .02, respectively). Conversely, there were no differences in PET parameters between lesions in SDHx+ patients and controls with low probability of SDHx+ mutations., Conclusions: FDG PET-CT has clinical utility in HNPGLs, mostly before local treatment. There were no significant differences in PET parameters between SDHx patients and a sporadic HNPGL population. However, regardless of SDHx mutation status, a high SUVmax was associated with more clinical events and prompts to a closer follow-up., (© 2021 John Wiley & Sons Ltd.)

Standard treatment for classical Hodgkin lymphoma (cHL) is poorly tolerated in older patients and results disappointing. We assessed safety and efficacy of brentuximab vedotin (BV), in previously untreated patients with cHL unfit for standard treatment due to age, frailty or comorbidity. The primary outcome was complete metabolic response (CMR) by positron emission tomography/computed tomography after four BV cycles (PET4). The secondary outcomes included progression-free survival (PFS), overall survival (OS), and toxicity. In all, 35 patients with a median age of 77 years and median total Cumulative Illness Rating Scale for Geriatrics (CIRS-G) score of 6 were evaluable for toxicity and 31 for response. A median of four cycles were given (range one-16). In all, 14 patients required dose reduction due to toxicity and 11 patients stopped treatment due to adverse events (AEs). A total of 716 AEs were reported, of which 626 (88%) were Grade 1/2 and 27 (77%) patients had at least one AE Grade ≥3. At PET4, CMR was 25·8% [95% confidence interval (CI) 13·7-42.2%] and objective response rate 83·9% (95% CI 63·7-90·8%). Median PFS was 7·3 months (95% CI 5·2-9·0), and OS 19·5 months. Our results suggest that BV monotherapy is tolerable but suboptimal in the front-line therapy of elderly or comorbid patients with cHL. Combining BV with other agents may be more effective. Trial Registration: Clinicaltrials.gov identifier: NCT02567851., (© 2020 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

Patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who are unfit for or relapsed postautologous stem-cell transplantation have poor outcomes. Historically, mTORC1 inhibitors have produced responses in approximately 30% of patients in this setting. mTORC1 inhibitor efficacy may be limited by resistance mechanisms including AKT activation by mTORC2. To date, dual mTORC1/2 inhibitors targeting both the TORC1 and TORC2 complexes have not been investigated in DLBCL. This phase II trial investigated the oral dual mTORC1/2 inhibitor vistusertib in an intermittent dosing schedule of 125 mg b.d. for 2 days per week. Thirty patients received vistusertib and six received vistusertib-rituximab for up to six cycles (28-day cycles). Two partial responses were achieved on monotherapy. Durations of response were 57 and 62 days, respectively, for these patients. 19% had stable disease within six cycles. In the monotherapy arm, the median progression-free survival was1.69 (95% confidence interval [CI] 1.61-2.14) months and median overall survival was 6.58 (95% CI 3.81-not reached) months, respectively. The median duration of response or stable disease across the trial duration was 153 days (95% CI 112-not reached). Tumour responses according to positron emission tomography/computed tomography versus computed tomography were concordant. There were no differences noted in tumour volume response according to cell of origin by either gene expression profiling or immunohistochemistry. Vistusertib ± rituximab was well tolerated; across 36 patients 86% of adverse events were grade (G) 1-2. Common vistusertib-related adverse events were similar to those described with mTORC1 inhibitors: nausea (47% G1-2), diarrhoea (27% G1-2, 6% G3), fatigue (30% G1-2, 3% G3), mucositis (25% G1-2, 6% G3), vomiting (17% G1-2), and dyspepsia (14% G1-2). Dual mTORC1/2 inhibitors do not clearly confer an advantage over mTORC1 inhibitors in relapsed or refractory DLBCL. Potential resistance mechanisms are discussed within., (© 2019 John Wiley & Sons, Ltd.)

Primary vulvar carcinoma is rare and thought to arise from either anogenital mammary-like glands or native apocrine sweat glands. The diagnosis is predominantly based on tumor morphology with supportive evidence from immunohistochemical staining and exclusion of a primary breast carcinoma. The primary modality of treatment is surgery, while optimal managment of advanced disease is unclear. We present the case of a lady who had metastatic recurrent apocrine carcinoma expressing estrogen receptors, who had a complete response assessed by PET-CT scanning after 7 months of tamoxifen therapy. The report includes a discussion of the histological diagnosis and assessment of response to treatment by PET-CT scanning.

Background: Interim PET scans in HIV-negative patients with Hodgkin lymphoma has emerged as one of the most important prognostic tools. However, equivalent studies in HIV-positive patients are yet to be performed., Objective: We evaluated the prognostic value of interim [18F]-fluoro-2-deoxy-D-glucose-PET (18F-FDG PET) after two or three cycles of chemotherapy using adriamycin, bleomycin, vinblastine and dacarbazine (ABVD) with concomitant HAART in HIV-positive patients with Hodgkin lymphoma., Methods: Patients with advanced HIV-Hodgkin lymphoma (HIV-HL) from six UK centres were included. Interim PET scans after two or three cycles of ABVD (PET-2 or PET-3) were carried out. Prognostic analysis correlated the 2-year progression-free survival (PFS) rate with the interim PET result., Results: Twenty-three evaluable patients were assessed, 21 achieved a negative interim PET and 22 achieved complete remission by computerized tomography scan criteria after ABVD therapy. After a median follow-up of 27 months (range 12-50), disease progression was seen in one patient. Treatment failure was seen in one of the two interim PET-positive patients and none of the interim PET-negative patients. The 2-year PFS for interim PET-positive patients was 50%, and 100% for interim PET-negative patients (P = 0.0012)., Conclusion: A negative interim 18F-FDG PET result is highly predictive of treatment success in HIV-HL patients.

Accurate staging of classical Hodgkin lymphoma (CHL) directs treatment intensity. Functional imaging can detect marrow/bone involvement making the role of bone marrow biopsy (BMB) unclear. We assessed current UK practice in CHL staging by questionnaire and retrospectively analyzed patients staged at a single center with BMB and (18)F-fluoro-2-deoxyglucose positron emission tomography/computed tomography (FDG-PET/CT). From 34 questionnaire responses 50% used FDG-PET/CT routinely. BMB was employed in 97% with advanced-stage and 30% of patients with limited-stage disease (70% of those not using routine FDG-PET/CT). Ten out of 50 patients were BM+, all of which were identified by FDG-PET/CT (PET+). Conventional BMB changed management in 2% of cases. There were no clinically significant FDG-PET/CT false positives. Conventional routine BMB staging in CHL is extremely insensitive. FDG-PET/CT can rule out marrow/bone involvement in CHL. In the FDG-PET/CT staging era BMB should be targeted to a minority of patients with FDG-PET/CT + bone/marrow uptake and only when management would be altered by the result.

Primary hepatic lymphoma is a rare presentation of a common disease. Diagnosis is difficult due to the risks of liver biopsy. We report the clinico-pathologic features of this presentation and specifically the utility of image-guided biopsy as a safe method of diagnosis. We retrospectively studied patients diagnosed with 'hepatic lymphoma' at a single center. Twenty-two patients fulfilled the criteria. Median age was 53 years (range 29-87). Nine patients were human immunodeficiency virus (HIV)-positive. The most frequent mode of presentation was with B-symptoms (15/22). All procedures were successful at obtaining diagnostic material with no complications. Six patients had synchronous bone marrow involvement. Nineteen patients received chemotherapy (10 had dose reductions) with an overall response rate of 74%. After a median follow-up of 19 months, 12 patients had died; the median overall survival (OS) was 4 months. Grade 3 or 4 aspartate transaminase (AST) abnormality was associated with very poor outcome. The OS of patients with hepatic lymphoma is poor. However, a response to modern induction therapies may predict a better outcome. The optimal dose adjustment of chemotherapy in this setting is unclear. In patients without readily accessible tissue, an image-guided core biopsy of hepatic lesions is a safe procedure with high diagnostic yield.

We report a case of regression of pulmonary and bony metastases in a patient with malignant melanoma following palliative treatment with systemic zoledronate and localised radiotherapy to the bone. Zoledronate is a potent new bisphosphonate used for the treatment of metabolic bone diseases including bone metastases due to its inhibitory effect on osteoclasts. In the context of metastatic cancer zoledronate is routinely used to improve bone pain and reduce the frequency of skeletal events. There is also an increasing body of evidence suggesting that bisphosphonates exhibit anti-tumour properties. Bisphosphonates are able to activate Vgamma9Vdelta2 gamma-delta T cells which can be key players in the immune defence against malignant cells. Furthermore bisphosphonates have direct anti-proliferative, anti-metastatic and pro-apoptotic effects on tumour cells. These actions, together with their low side effect profile, may prove to be useful therapeutic tools in the treatment of cancer even in the absence of bone metastases. On the basis of this case report we here review the current literature on present preclinical and clinical studies using bisphosphonates for the treatment of cancer.