Utilizing clinical, pathological and radiological information to guide postoperative radiotherapy in prostate cancer.

INTRODUCTION: A detectable and rising PSA following radical prostatectomy is indicative of recurrent prostate cancer. Salvage radiotherapy (SRT) with/without androgen deprivation therapy represents the main treatment option for these patients and has been historically associated with a biochemical control rate of ~70%. To determine the optimal timing, diagnostic workup, radiotherapy dosefractionation, treatment volume, and use of systemic therapy, several informative studies have been conducted in the last decade. AREAS COVERED: This review examines the recent evidence to guide radiotherapy decision making in the SRT setting. Key topics include adjuvant vs salvage RT, utilization of molecular imaging and genomic classifiers, length of androgen deprivation therapy, inclusion of elective pelvic volume, and emerging role for hypofractionation. EXPERT OPINION: Recently reported trials, conducted in an era prior to the routine use of molecular imaging and genomic classifiers, have been pivotal in establishing the current standard of care for SRT in prostate cancer. However, decisions about radiation treatment and systemic therapy may be tailored based on available prognostic and predictive biomarkers. Data from contemporary clinical trials are awaited to define and establish individualized, biomarker-driven approaches for SRT.

Stability Matters: Radiochemical Stability of Therapeutic Radiopharmaceutical 177Lu-PSMA I&T.

Labeling radiopharmaceuticals and testing the quality of the labeled product before injecting it into patients are standard operating procedures in the nuclear medicine department. There is a different shelf life for each labeled product, which determines how long a product can maintain in vitro stability before it needs to be discarded. 177Lu is a radioactive isotope that is increasingly being accepted into the treatment paradigm for palliation of advanced-stage tumors, including metastatic castration-resistant prostate cancer (mCRPC) and neuroendocrine tumors (NETs). In our institution, synthesis of 177Lu with prostate-specific membrane antigen imaging and therapy (PSMA I&T) for palliation of mCRPC is performed on an automated synthesis system. Methods: After each synthesis, the final product quality was evaluated by high-performance liquid chromatography (HPLC) and instant thin-layer chromatography (ITLC) at 3 different time points: 0, 24, and 48 h. Between February 2020 and October 2020, the quality of 35 batches of 177Lu-PSMA I&T was evaluated. Results: The average radiochemical purity of ITLC-silica gel was found to be greater than 99% (99.70% ± 0.05%), and HPLC was greater than 98% (98.60% ± 0.05%). Conclusion: Our findings demonstrate that synthesis of 177Lu-PSMA I&T with an automated synthesis system can remain stable for 48 h after labeling.

Utility of Ga68 prostate-specific membrane antigen positron-emission tomography for pre-operative staging of high-risk prostate cancer in a prospective cohort.

INTRODUCTION: To assess the yield of Ga68 PSMA PET/CT added to the conventional staging of high-risk prostate cancer in terms of altered staging and changes to management. METHODS: Patients with high-risk prostate cancer without metastatic disease on conventional staging referred for Ga68 PSMA PET/CT at Mercy Radiology, Auckland, New Zealand, were prospectively recruited. Conventional staging was double read in a blinded fashion by oncology fellowship-trained radiologists, who were also experienced in PET/CT, followed by interpretation of the PSMA PET/CT by the same radiologists. Confirmation of changes in management decision was obtained from the treating surgeon and multidisciplinary team meeting records. Ethical approval was obtained from the Health and Disability Ethics Committee. All patients gave written informed consent. RESULTS: A total of 49 patients were scanned. Three who were otherwise eligible for radical prostatectomy elected alternative treatments, leaving 46 patients included for analysis in the study. The addition of PSMA PET/CT was associated with highly statistically significant changes in both staging and management. The stage was changed in 32.6% (95% CI 20.8-47.1%, P < 0.001) patients upstaging in 60% and downstaging in 40%; clinical management in 34.8% (95% CI 22.6-49.3%; P < 0.001), with intramodality change in 25% and intermodality change in 75%. Factors predictive of a change in management with PSMA PET/CT included higher Gleason score and a greater proportion of prostatic cores positive for tumour. CONCLUSION: The addition of Ga68 PSMA PET/CT to conventional staging in high-risk prostate cancer frequently leads to changes in staging and management.

A case of large cell neuroendocrine carcinoma of the bladder with prolonged spontaneous remission.

Large cell neuroendocrine carcinoma (LCNEC) of the urinary bladder are rare. We present a case of a 72-year-old man who presented with back pain and acute renal failure. Ultrasound showed a soft tissue mass in the base of the bladder causing bilateral ureteric obstruction. Subsequent biopsy of this mass demonstrated neuroendocrine carcinoma. He was commenced on neoadjuvant chemotherapy (carboplatin/etoposide) and proceeded to a radical cysto-prostatectomy. Histology revealed a LCNEC involving the bladder, T4a with invasion through to adipose tissue and posteriorly at perivesical resection margins. In addition, there was a Gleason score 9 prostatic adenocarcinoma, distinct from the neuroendocrine carcinoma. Following surgery, the patient developed gross local-regional recurrence and refused further systemic therapy. However, 1 year following referral to palliative care, a further CT-PET showed complete spontaneous remission of his disease. There are only few case reports of LCNEC of the urinary bladder therefore the pathogenesis and treatment protocol are still unclear. This case report highlights the unpredictable nature of this disease.

Indeterminate CT pulmonary angiogram: Why and does it matter?

INTRODUCTION: This study assessed the rate of indeterminate CT pulmonary angiogram (CTPA) in a general hospital and evaluated potential contributing factors to an indeterminate CTPA and patients' eventual clinical outcome. METHODS: Four hundred and three consecutive CTPA and their finalised report from 01/08/2012 to 05/12/2012 at Waitemata DHB were reviewed retrospectively. Patient demographics, scan parameters and average Hounsfield unit (HU) of the main pulmonary trunk (PT) and likely cause of indeterminate study were documented. Studies were categorised into diagnostic, suboptimal or non-diagnostic studies. Univariate and multiple regression analyses were employed. RESULTS: Six per cent (n = 24) of the studies were deemed indeterminate which included suboptimal and non-diagnostic studies. Seven pregnant patients were scanned during the study period and four of the seven studies were deemed indeterminate. In univariate analysis, predictors of indeterminate studies included 'weight' (P = 0.022), 'average HU of PT' (P < 0.0001) and 'effective dose' (P = 0.0003). In the multivariate logistic regression model, only 'average HU of PT' was associated with indeterminate studies (OR = 0.99, 95%CI: 0.99, 1.00). Twelve of 24 indeterminate studies had suboptimal pulmonary enhancement with causes including suboptimal timing of contrast bolus, hyperdynamic state due to pregnancy and transient interruption of contrast. Three patients had excessive noise due to body habitus. Eight studies had motion artefacts and one patient had left lower lobe pneumonia which decreased the accuracy. A third of the indeterminate studies were clinically considered as negative by referring clinicians. CONCLUSIONS: Pulmonary trunk average Hounsfield unit is a predictor of indeterminate CT pulmonary angiogram.

The relative prognostic utility of standardized uptake value, gross tumor volume, and metabolic tumor volume in oropharyngeal cancer patients treated with platinum based concurrent chemoradiation with a pre-treatment [(18)F] fluorodeoxyglucose positron emission tomography scan.

OBJECTIVES: This study compared the relative prognostic utility of the Gross Tumor Volume (GTV), maximum Standardized Uptake Value (SUVmax), and Metabolic Tumor Volume (MTV) in a uniform cohort of oropharyngeal squamous cell carcinoma (OPSCC) patients treated with platinum-based concurrent chemoradiation therapy (CCRT). METHODS AND MATERIALS: One-hundred OPSCC with a pretreatment [(18)F] fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET-CT) were treated with CCRT. Kaplan-Meier curves and Cox proportional hazard models were generated. RESULTS: When dichotomized by the median, a smaller MTV correlated with improved 5year locoregional control (LRC) (98.0% versus 87.0%, p=0.049), freedom from distant metastasis (FDM) (91.7% versus 65.0%, p=0.005), progression-free survival (PFS) (80.3% versus 56.7%, p=0.015), and overall survival (OS) (84.1% versus 57.8%, p=0.008), whereas a smaller GTV correlated with improved PFS (80.3% versus 57.4%, p=0.040) and OS (82.1% versus 60.1%, p=0.025). SUVmax failed to correlate with any outcome. On multivariate analysis, when adjusted for GTV, T-stage, and N-stage a smaller MTV remained independently correlated with improved FDM, PFS, and OS. GTV failed to reach significance in the multivariate model. CONCLUSIONS: A smaller MTV correlates with improved LRC, FDM, PFS, and OS in OPSCC patients undergoing platinum-based CCRT.

A prospective study of ¹8FDG-PET with CT coregistration for radiation treatment planning of lymphomas and other hematologic malignancies.

PURPOSE: This prospective single-institution study examined the impact of positron emission tomography (PET) with the use of 2-[(18)F] fluoro-2-deoxyglucose and computed tomography (CT) scan radiation treatment planning (TP) on target volume definition in lymphoma. METHODS AND MATERIALS: 118 patients underwent PET/CT TP during June 2007 to May 2009. Gross tumor volume (GTV) was contoured on CT-only and PET/CT studies by radiation oncologists (ROs) and nuclear medicine physicians (NMPs) for 95 patients with positive PET scans. Treatment plans and dose-volume histograms were generated for CT-only and PET/CT for 95 evaluable sites. Paired t test statistics and Pearson correlation coefficients were used for analysis. RESULTS: 70 (74%) patients had non-Hodgkin lymphoma, 10 (11%) had Hodgkin lymphoma, 12 (10%) had plasma-cell neoplasm, and 3 (3%) had other hematologic malignancies. Forty-three (45%) presented with relapsed/refractory disease. Forty-five (47%) received no prior chemotherapy. The addition of PET increased GTV as defined by ROs in 38 patients (median, 27%; range, 5%-70%) and decreased GTV in 41 (median, 39.5%; range, 5%-80%). The addition of PET increased GTV as defined by NMPs in 27 patients (median, 26.5%; range, 5%-95%) and decreased GTV in 52 (median, 70%; range, 5%-99%). The intraobserver correlation between CT-GTV and PET-GTV was higher for ROs than for NMPs (0.94, P<.01 vs 0.89, P<.01). On the basis of Bland-Altman plots, the PET-GTVs defined by ROs were larger than those defined by NMPs. On evaluation of clinical TPs, only 4 (4%) patients had inadequate target coverage (D95 <95%) of the PET-GTV defined by NMPs. CONCLUSIONS: Significant differences between the RO and NMP volumes were identified when PET was coregistered to CT for radiation planning. Despite this, the PET-GTV defined by ROs and NMPs received acceptable prescription dose in nearly all patients. However, given the potential for a marginal miss, consultation with an experienced PET reader is highly encouraged when PET/CT volumes are delineated, particularly for questionable lesions and to assure complete and accurate target volume coverage.

18F-fluorodeoxyglucose positron emission tomography in the staging and prognosis of T cell lymphoma.

We previously reported that (18)F-fluorodeoxyglucose positron emission tomography scan (FDG-PET) is almost universally positive in patients with T cell lymphoma. In the present analysis we examined the impact of FDG-PET on the initial staging of peripheral T cell lymphomas (PTCLs), and the prognostic value of interim FDG-PET. This retrospective analysis identified patients with mature T or natural killer (NK) lymphomas who had PET scans as part of initial staging or staging at relapse [(n = 95) (staging cohort)] in the PTCL database at Memorial Sloan-Kettering Cancer Center. A subset of these patients had repeat PET for interim restaging during initial therapy with curative intent [(n = 50) (interim restaging cohort)]. The frequency of specific T cell histologies included in this analysis were: PTCL not otherwise specified (NOS) (n = 35); angioimmunoblastic T cell lymphoma (AITL) (n = 17); anaplastic large cell lymphoma (ALCL), ALK-1+ (n = 11) and ALK-1- (n = 12); adult T cell lymphoma/leukemia (ATLL) (n = 7); NK/T cell lymphoma (NKTCL) (n = 10); and enteropathy-associated T cell lymphoma (EATL) (n = 3). In the staging cohort, 77 patients were newly diagnosed, and 18 had relapsed disease. Pretreatment FDG-PET was positive in 96% of patients. PET identified additional disease sites in 47/95 patients (50%) when added to conventional staging. Most frequently identified additional sites were: other nodal (n = 24); bone (n = 10); skin (n = 8); nasopharynx (n = 4); spleen (n = 3); and lung (n = 2). However, FDG-PET modified computed tomography (CT)-based staging in only 5/95 patients (5.2%): two patients were upstaged and three patients were downstaged. FDG-PET-based staging did not alter planned treatment for any patient. Interim restaging with PET was performed after a median of 4 cycles of chemotherapy. In this cohort, treatment regimens included cyclophosphamide, doxorubicin, vincristine and prednisone CHOP (n = 19); CHOP/ifosfamide, carboplatin and etoposide (ICE) (n = 26); and other (n = 7). Subsequently, 29 patients were consolidated with either autologous (n = 22) or allogeneic (n = 7) stem cell transplant. After a median follow-up of 3.4 years for surviving patients, those with negative interim PET had superior progression-free survival (PFS) compared to patients with positive interim PET (p = 0.03). There were no differences in overall survival (OS). In PTCL, FDG-PET commonly identifies additional sites of disease but infrequently impacts CT-based staging and does not influence therapy. Interim FDG-PET may predict for PFS. FDG-PET should be integrated into prospective trials to confirm these findings.

ABVD alone and a PET scan complete remission negates the need for radiologic surveillance in early-stage, nonbulky Hodgkin lymphoma.

BACKGROUND: Patients with early-stage, nonbulky classic Hodgkin lymphoma (cHL) undergo intensive posttreatment radiologic surveillance despite having a low risk of disease recurrence. The current study attempted to evaluate the risk of disease recurrence and the value of radiologic surveillance in patients treated with the combination of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) alone who achieved a complete remission (CR) as noted on posttreatment positron emission tomography (PET). METHODS: Forty-seven patients who underwent therapy with interim and/or posttreatment PET scans were evaluated for disease recurrence during ≥ 24 months of follow-up. Their presenting characteristics and imaging results were assessed and interpreted in relation to clinical outcome. RESULTS: All 47 patients were eligible for analysis. The majority of patients were female (35 patients) with a median age of 28 years (range, 17 years-65 years.). The nodular sclerosing subtype was the predominant histology (41 patients). A total of 34 patients were staged with IIA disease, 6 with IA disease, 6 with IIB disease, and 1 with IIEA disease (lung) (according to Cotswolds modification of the Ann Arbor staging system). All patients completed 6 cycles of planned ABVD therapy and achieved a CR. Two had a positive PET scan (1 interim scan and 1 posttreatment scan); both were biopsy-proven sarcoidosis. Two patients developed disease recurrence at 7 months and 24 months, respectively, after negative interim and posttreatment imaging. One case of recurrence was identified through surveillance imaging and the other was identified simultaneously by the patient and surveillance scan. A total of 45 patients experienced a durable CR; 21 had additional unscheduled imaging/workup during surveillance to investigate symptoms or imaging signs of concern. CONCLUSIONS: Because of a low risk of disease recurrence, posttreatment radiologic surveillance appears to be unnecessary in patients with early-stage, nonbulky (CD20 negative) cHL who achieve a PET-detected CR with the ABVD combination alone. This will reduce cumulative radiation exposure and health care costs in a predominantly young patient population.

18F-FDG PET/CT metabolic tumor volume and total lesion glycolysis predict outcome in oropharyngeal squamous cell carcinoma.

UNLABELLED: Treatment of oropharyngeal squamous cell carcinoma with chemoradiotherapy can now accomplish excellent locoregional disease control, but patient overall survival (OS) remains limited by development of distant metastases (DM). We investigated the prognostic value of staging (18)F-FDG PET/CT, beyond clinical risk factors, for predicting DM and OS in 176 patients after definitive chemoradiotherapy. METHODS: The PET parameters maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were recorded. Univariate Cox regression was used to examine the prognostic value of these variables and clinical prognosticators for local treatment failure (LTF), OS, and DM. Multivariate analysis examined the effect of SUVmax, TLG, and MTV in the presence of other covariates. Kaplan-Meier curves were used to evaluate prognostic values of PET/CT parameters. RESULTS: Primary tumors were distributed across all stages. Most patients underwent chemoradiotherapy only, and 11 also underwent tonsillectomy. On univariate analysis, primary tumor MTV was predictive of LTF (P = 0.005, hazard ratio [HR] = 2.4 for a doubling of MTV), DM and OS (P < 0.001 for both, HR = 1.9 and 1.8, respectively). The primary tumor TLG was associated with DM and OS (P < 0.001, HR = 1.6 and 1.7, respectively, for a doubling of TLG). The primary tumor SUVmax was associated with death (P = 0.029, HR = 1.1 for a 1-unit increase in standardized uptake value) but had no relationship with LTF or DM. In multivariate analysis, TLG and MTV remained associated with death after correcting for T stage (P = 0.0125 and 0.0324, respectively) whereas no relationship was seen between standardized uptake value and death after adjusting for T stage (P = 0.158). CONCLUSION: Parameters capturing the volume of (18)F-FDG-positive disease (MTV or TLG) provide important prognostic information in oropharyngeal squamous cell carcinoma treated with chemoradiotherapy and should be considered for risk stratification in this disease.

18F-FDG uptake in metaphyseal growth arrest lines: a case study.

Growth arrest lines (also referred to as Harris lines) refer to dense metaphyseal trabecular lines, perpendicular to the long axis of the bone. The phenomenon is seen only in patients with immature skeletal structure after periods of nutritional insufficiency, illness, and prolonged immobilization or bisphosphonates administration during which bone growth is inhibited. With resumption of bone growth, a dense trabecular line becomes visible, typically at the metaphyses of rapidly growing long bone. We describe 18F-FDG uptake in the growth arrest lines of a 7-year-old boy treated for left distal tibial osteosarcoma.

Assessment of therapy responses and prediction of survival in malignant pleural mesothelioma through computer-aided volumetric measurement on computed tomography scans.

PURPOSE: The purposes of this study were (1) to calculate the tumor volume in patients with malignant pleural mesothelioma using computed tomography (CT) scan images and a computer-aided measurement technique and (2) to investigate whether the baseline volume, or volume change after chemotherapy, predicts patient survival. METHODS: We compiled the clinical characteristics and outcome from 30 patients enrolled in two clinical trials at our cancer center in which the patients were treated with induction chemotherapy followed by surgery and radiation. CT scans of 30 patients were obtained at baseline and after two cycles of chemotherapy. Tumor volumes were calculated using a semiautomated computer algorithm. Overall survival was measured using a landmark time at 3 months post-treatment start date such that all patients had already received two cycles of chemotherapy and a follow-up scan. Association of volume changes with overall survival were determined by a Cox Proportional Hazards Model or log-rank test. The relationship between both pre and postoperative clinical stage and baseline tumor volume was analyzed using the rank sum test. RESULTS: The median baseline tumor volume was 473 cm(3) (range, 61 cm(3)-2108 cm(3)). Patients with high preoperative stages (III and IV) had larger baseline tumor volume than those with low preoperative stages (I and II) (p = 0.05). Patients with baseline volumes smaller than 619 cm(3) tended to survive longer than those with baseline volumes larger than or equal to 619 cm(3) (p = 0.07). Percentage change of tumor volume from baseline to first follow-up CT after two cycles of chemotherapy was significantly associated with overall survival (hazard ratio: 1.94 [95% confidence interval, 1.05-3.60], p = 0.04). Whereas the relative change in modified RECIST measurements was not significantly associated with overall survival (hazard ratio: 1.06 [95% confidence interval, 0.96-1.16], p = 0.25). By classifying changes of tumor volumes between two scans into two groups, i.e., "increase" and "decrease," a significant difference in survival was found between those who increased and decreased after two cycles of chemotherapy (p = 0.03). CONCLUSIONS: Changes in tumor volume after two cycles of chemotherapy predicted overall survival in patients with malignant pleural mesothelioma. Tumor volume at baseline was shown to be associated with preoperative clinical stage and survival. Computer-aided volumetric measurements may enable more reliable therapeutic response assessment and could provide additional prognostic information.

Tricuspid valve replacement: bioprosthetic or mechanical valve?

Significant morbidity and mortality is associated with tricuspid valve replacement, and controversy still exists as to the ideal prosthesis in this position. This study aimed to identify the risk factors for low cardiac output and mortality, and whether bioprosthetic or mechanical valves perform better in the tricuspid position. Results of 121 tricuspid valve replacements in 104 patients between January 1966 and December 2002 were reviewed. Most patients were in New York Heart Association functional class III or IV. Perioperative mortality was 19%. On multivariate analysis, age and preoperative jaundice were significant predictors of low cardiac output; age, jaundice, atrial fibrillation, and bypass time were significant predictors of mortality. Mechanical valves were significantly more prone to thromboembolism, whereas bioprostheses suffered structural valve deterioration. There were no significant differences in anticoagulation or bleeding episodes between the two groups, nor in valve-related events, deaths, and long term survival. There was no significant difference in performance so as to recommend one type over the other, but bioprosthetic valves may be more favorable as they fail predictably.

Coronary artery bypass grafting in an immune thrombocytopenic purpura patient using off-pump techniques.

We performed an off-pump coronary artery bypass grafting (OPCABG) procedure on a 60-year-old woman with idiopathic thrombocytopenic purpura (ITP) whose platelet count was 42 x 10(3) per microliter on admission. She was treated with immunoglobulin G (IgG) (0.5 g.kg(-1).d(-1)) for 4 days, resulting in a platelet count rise to 187 x 10(3) per microliter. She subsequently underwent an uneventful OPCABG procedure without requiring any blood transfusions. The combination of OPCABG and preoperative IgG therapy appears to be an ideal strategy for ITP patients requiring coronary revascularization.