Post-treatment Response Assessment Research Articles

Manual and Semi-Automated Measurement and Calculation of Osteosarcoma Treatment Effect Using Whole Slide Image and Qupath.

In osteosarcoma, the most significant indicator of prognosis is the histologic changes related to tumor response to preoperative chemotherapy, such as necrosis. We have developed a method to measure the osteosarcoma treatment effect using whole slide image (WSI) with an open-source digital image analytical software Qupath. In Qupath, each osteosarcoma case was treated as a project. All H&E slides from the entire representative slice of osteosarcoma were scanned into WSIs and imported into a project in Qupath. The regions of tumor and tumor necrosis were annotated, and their areas were measured in Qupath. In order to measure the osteosarcoma treatment effect, we needed to calculate the percentage of total necrosis area over total tumor area. We developed a tool that can automatically extract all values of tumor and necrosis areas from a Qupath project into an Excel file, sum these values for necrosis and whole tumor respectively, and calculate necrosis/tumor percentage. Our method that combines WSI with Qupath can provide an objective measurement to facilitate pathologist's assessment of osteosarcoma response to treatment. The proposed approach can also be used for other types of tumors that have clinical need for post-treatment response assessment.

From planned neck dissection to PET response to circulating tumour DNA: changes in post-treatment assessment of HPV-driven oropharyngeal cancer†.

Circulating tumour human papillomavirus DNA (ctHPVDNA) is an emerging tool to assess post-treatment response in patients with HPV+ oropharyngeal squamous cell carcinoma (OPSCC). Its use is not a standard practice, however, with interval F-18 FDG PET/CT and fiberoptic examination preferred. Post-treatment PET/CT at 3 months has a low positive predictive value (PPV), especially in patients with HPV+ OPSCC treated with (chemo)radiation therapy (CRT). We aimed to compare 3-6 month post-treatment PET/CT and ctHPVDNA test results to determine the most effective option for post-treatment response assessment. Patients with HPV+ OPSCC that underwent commercially available ctHPVDNA blood testing after curative intent treatment were identified. Demographic, clinical, treatment, surveillance and oncologic outcome information were collected for each patient. Specificity and false positive rate were calculated for post-treatment PET/CT and ctHPVDNA. 80% of patients had Stage I disease. 52% of the population was treated with definitive chemoradiation (43%) or accelerated radiation (9%), with the remaining patients treated with transoral robotic surgery (TORS) +/- risk-adapted adjuvant therapy. In total, 25 patients underwent ctHPVDNA testing and PET/CT at 3-6 months after finishing treatment. At 3-6 months post-treatment, specificity of ctHPVDNA and PET/CT was 96% and 56%, correlating to false positive rates of 4% and 44%, respectively. ctHPVDNA is more reliable than PET/CT following treatment in patients with HPV+ OPSCC, and its incorporation in post-treatment response assessment will decrease the rate of anxiety over persistent disease and lead to a decrease in unnecessary medical procedures, including completion of neck dissection.

Early post-treatment MRI predicts long-term hepatocellular carcinoma response to radiation segmentectomy

ObjectivesRadiation segmentectomy using yttrium-90 plays an emerging role in the management of early-stage HCC. However, the value of early post-treatment MRI for response assessment is uncertain. We assessed the value of response criteria obtained early after radiation segmentectomy in predicting long-term response in patients with HCC.Materials and methodsPatients with HCC who underwent contrast-enhanced MRI before, early, and 12 months after radiation segmentectomy were included in this retrospective single-center study. Three independent radiologists reviewed images at baseline and 1st follow-up after radiation segmentectomy and assessed lesion-based response according to mRECIST, LI-RADS treatment response algorithm (TRA), and image subtraction. The endpoint was response at 12 months based on consensus readout of two separate radiologists. Diagnostic accuracy for predicting complete response (CR) at 12 months based on the 1st post-treatment MRI was calculated.ResultsEighty patients (M/F 60/20, mean age 67.7 years) with 80 HCCs were assessed (median size baseline, 1.8 cm [IQR, 1.4–2.9 cm]). At 12 months, 74 patients were classified as CR (92.5%), 5 as partial response (6.3%), and 1 as progressive disease (1.2%). Diagnostic accuracy for predicting CR was fair to good for all readers with excellent positive predictive value (PPV): mRECIST (range between 3 readers, accuracy: 0.763–0.825, PPV: 0.966–1), LI-RADS TRA (accuracy: 0.700–0.825, PPV: 0.983–1), and subtraction (accuracy: 0.775–0.825, PPV: 0.967–1), with no difference in accuracy between criteria (p range 0.053 to > 0.9).ConclusionmRECIST, LI-RADS TRA, and subtraction obtained on early post-treatment MRI show similar performance for predicting long-term response in patients with HCC treated with radiation segmentectomy.Clinical relevance statementResponse assessment extracted from early post-treatment MRI after radiation segmentectomy predicts complete response in patients with HCC with high PPV (≥ 0.96).Key Points• Early post-treatment response assessment on MRI predicts response in patients with HCC treated with radiation segmentectomy with fair to good accuracy and excellent positive predictive value.• There was no difference in diagnostic accuracy between mRECIST, LI-RADS, and subtraction for predicting HCC response to radiation segmentectomy.

Investigation of response factors for monotherapy with immune checkpoint inhibitors in non-small cell lung cancer patients with PD-L1 expression

Immune checkpoint inhibitor (ICI) monotherapy is currently approved for the treatment of advanced non-small cell lung cancer (NSCLC) patients with programmed death ligand-1 (PD-L1) expression ≥50%. However, the efficacy of ICI monotherapy in patients with PD-L1 expression <50% has not yet been fully elucidated. The aim of this study was to identify the clinical characteristics of NSCLC patients with PD-L1 expression <50% who respond to single-agent ICIs and factors that predict response. Patients with advanced or recurrent NSCLC with a PD-L1 tumor proportion score (TPS) of 50% or less who received new monotherapy with an ICI between July 2012 and December 2022 were retrospectively analyzed. Patients with response were compared with those without response in the post-treatment response assessment. Among the 37 patients, six (16.2%) NSCLC patients in the response group responded to ICI monotherapy and had a significantly lower body mass index (BMI) (p = 0.003). Significantly more patients in the response group developed immune-related adverse events (irAEs) than in the nonresponse group (p < 0.001). Multivariate analysis identified high BMI as a significant independent risk factor predicting nonresponse to ICI monotherapy in NSCLC patients with PD-L1 < 50%. Among NSCLC patients with PD-L1 < 50%, those with a higher BMI were more likely to be nonresponders to ICI monotherapy. In addition, the group that responded to ICI monotherapy may have been at higher risk of developing irAEs, suggesting that careful follow-up is warranted.

Eprenetapopt combined with venetoclax and azacitidine in TP53-mutated acute myeloid leukaemia: a phase 1, dose-finding and expansion study

TP53-mutated acute myeloid leukaemia is associated with poor outcomes. Eprenetapopt (APR-246) is a first-in-class, small-molecule p53 reactivator. We aimed to evaluate the combination of eprenetapopt and venetoclax with or without azacitidine in patients with TP53-mutated acute myeloid leukaemia. This phase 1, multicentre, open-label, dose-finding and cohort expansion study was done at eight academic research hospitals in the USA. Inclusion criteria were age of at least 18 years; at least one pathogenic TP53 mutation; treatment-naive acute myeloid leukaemia according to the 2016 WHO classification; an ECOG performance status of 0-2; and a life expectancy of at least 12 weeks. In dose-finding cohort 1 patients received previous therapy with hypomethylating agents for myelodysplastic syndromes. In dose-finding cohort 2, previous use of hypomethylating agents was not permitted. Treatment cycles were 28 days. Patients in cohort 1 received intravenous eprenetapopt 4·5 g/day on days 1-4 and oral venetoclax 400 mg/day on days 1-28; those in cohort 2 also received subcutaneous or intravenous azacitidine 75 mg/m2 on days 1-7. The expansion part of the study proceeded with patients enrolled as in cohort 2. Primary endpoints were safety in all cohorts (assessed in patients receiving at least one dose of assigned treatment) and complete response in the expansion cohort (assessed in patients who completed at least one treatment cycle and had at least one post-treatment clinical response assessment). The trial is registered with ClinicalTrials.gov, NCT04214860, and is complete. Between Jan 3, 2020, and July 22, 2021, 49 patients were enrolled across all cohorts. Six patients were initially enrolled into each of dose-finding cohorts 1 and 2; after no dose-limiting toxicities were observed, cohort 2 was expanded to enrol an additional 37 patients. The median age was 67 years (IQR 59-73). 24 (49%) of 49 patients were female and 25 (51%) male, and 40 (82%) were White. At data cutoff (Oct 1, 2021), the median length of follow-up was 9·5 months (IQR 6·1-11·5). No dose-limiting toxicities were recorded and the recommended phase 2 dose for eprenetapopt combinations was 4·5 g/day on days 1-4. Across all patients, adverse events of grade 3 or worse occurring in at least 20% of patients were febrile neutropenia (23 [47%] of 49 patients), thrombocytopenia (18 [37%] patients), leukopenia (12 [25%] patients), and anaemia (11 [22%] patients). Treatment-related serious adverse events occurred in 13 (27%) of 49 patients and there was one (2%) treatment-related death (sepsis). 25 (64%, 95% CI 47-79) of 39 patients had an overall response with eprenetapopt and venetoclax with azacytidine; 15 (38%, 23-55) had a complete response. Eprenetapopt and venetoclax with azacitidine had an acceptable safety profile and encouraging activity, supporting further frontline evaluation of this combination in the treatment of TP53-mutated acute myeloid leukaemia. Aprea Therapeutics.

Diagnostic Performance of Response Assessment FDG-PET/CECT in HNSCC Treated With Definitive Radio(chemo)therapy Using NI-RADS.

To assess the diagnostic performance of response assessment 18F-fluorodeoxyglucose positron emission tomography/contrast-enhanced computed tomography (FDG-PET/CECT) following definitive radio(chemo)therapy in head and neck squamous cell carcinoma (HNSCC) using Neck Imaging Reporting and Data System (NI-RADS). A retrospective analysis from a prospectively maintained dataset. Tertiary-care comprehensive cancer center in a low-middle-income country. Adults with newly diagnosed, biopsy-proven, nonmetastatic HNSCC treated with definitive radio(chemo)therapy were included. Posttreatment response assessment FDG-PET/CECT scans were retrospectively assigned NI-RADS categories (1-3) for the primary site, neck, and both sites combined. Locoregional recurrence occurring within 2-years was defined as the event of interest. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and overall accuracy were calculated. Locoregional control stratified by NI-RADS categories was computed with the Kaplan-Meier method and compared using the log-rank test. Posttreatment FDG-PET/CECT scans were available in 190 patients constituting the present study cohort. Sensitivity, specificity, PPV, NPV, and overall accuracy of the NI-RADS template for the primary site was 73.5%, 81.4%, 46.3%, 93.4%, and 80.0%, respectively. Similar metrics for the neck were 72.7%, 87.5%, 43.2%, 96.1%, and 85.8%, respectively. Combining primary site and neck, the corresponding metrics of diagnostic accuracy were 84.4%, 69.7%, 46.3%, 93.5%, and 73.2%, respectively. At a median follow-up of 40 months, Kaplan-Meier estimates of 2-year locoregional control were significantly higher for NI-RADS category 1 (94.2%) compared to NI-RADS category 2 (69.4%) and category 3 (20.4%), respectively (stratified log-rank p < .0001). FDG-PET/CECT using the NI-RADS template is associated with good diagnostic performance and prognostic utility in HNSCC treated with definitive radio(chemo)therapy.

Changes in the Ultrastructure of the Bladder Urothelium in Patients with Interstitial Cystitis after Intravesical Injections of Platelet-Rich Plasma.

Urothelial dysfunction is considered a key pathological mechanism of interstitial cystitis/bladder pain syndrome (IC/BPS). Intravesical platelet-rich plasma (PRP) injections might be effective for treating IC/BPS. This prospective study investigated the changes in electron microscopic findings among IC/BPS patients after intravesical PRP injections. Twenty-six patients with refractory non-ulcer IC/BPS underwent monthly intravesical PRP injections for 4 months. Changes in clinical symptom scores and video urodynamic study parameters were assessed from baseline to after the PRP injections. A post-treatment Global Response Assessment (GRA) score ≥ 2 was considered a successful outcome. The mean GRA score was significantly higher after 4 PRP injections than at baseline. Approximately 42% of patients experienced successful outcomes after PRP treatment. Urothelial ultrastructural defects showed no significant differences between baseline and after the PRP injections. However, patients showed variable improvements in different urothelial defects (grade improvements: urothelium cell layers, 31%; umbrella cell integrity, 42%; umbrella cell surface uroplakin plaque, 54%; tight junctions between adjacent umbrella cells, 46%; lysed organelles, 58%; inflammatory cell infiltration, 31%). Patients with successful treatment outcomes showed significant improvements in urothelial tight junction defects. Repeated intravesical PRP injections are effective for improving IC/BPS symptoms as they promote urothelial ultrastructural defect recovery.

Pharmacist-led drug therapy management for hepatitis C at a federally qualified health care center

BackgroundChronic hepatitis C (HCV) infection is challenging to address in patients with barriers to accessing care, including those from underserved populations. Linking at-risk patients through the HCV cascade of care can address such disparities by leveraging existing patient–provider relationships to identify and treat HCV. Pharmacists are ideal clinical team members to provide direct-acting antiviral (DAA) management, given their expertise in pharmacotherapy and medication access. However, literature describing pharmacist-led DAA management at federally qualified health centers (FQHCs) is limited. Objective(s)To describe HCV screening, DAA prescribing and treatment initiation, post-treatment sustained virologic response (SVR) assessment, and treatment outcomes in an FQHC with pharmacist-led DAA management. MethodsThis study describes HCV screening rates in adults with select HCV risk factors receiving primary care at a Midwest FQHC over a 4-year period. In patients with a detectible HCV viral load, DAA prescription orders for patients referred to pharmacist-led DAA management was evaluated in comparison with usual care. Treatment completion and SVR results were assessed in patients referred to pharmacists. ResultsHCV screening in patients with identifiable risk factors increased from 8.0% to 67.5% over 4 years, driven by a clinical reminder for HCV screening in the birth year cohort. Of patients with positive HCV viral load results, 9.9% in the usual care group received an order for DAA therapy versus 57.1% (P < 0.001) in the pharmacist-led DAA management group. Of 162 patients referred to pharmacist-led DAA management, 61 (37.7%) initiated therapy. Of patients who initiated treatment, 57 (94.7%) had post-treatment viral load testing, with 46 (80.7% of treated patients) having SVR results and 45 (97.8% of SVR tested patients) testing negative. No usual care patients had subsequent negative HCV viral load results. ConclusionPharmacist-led DAA management is an effective intervention to improve the treatment of patients with HCV in the FQHC setting.

The Efficacy and Mid-term Durability of Urethral Sphincter Injections of Platelet-Rich Plasma in Treatment of Female Stress Urinary Incontinence.

Aims: This study investigated the therapeutic effect of repeated urethral sphincter injections of autologous platelet-rich plasma (PRP) in treatment of stress urinary incontinence (SUI) in women due to intrinsic sphincter deficiency (ISD) refractory to medical treatment or after the first anti-incontinence surgery. Methods: Twenty-six women with SUI due to urodynamically proven ISD were prospectively enrolled. Five milliliters of PRP (2.5–5 times of the platelet concentrations in peripheral blood) were injected into the external sphincter at 5 sites, with 4 treatments at monthly interval. The primary end-point was post-treatment Global Response Assessment (GRA, scored 0–3) score after four PRP treatments. A GRA ≥ 2 was considered as a successful result. The secondary endpoints included changes in visual analog scale (VAS) of SUI and urodynamic parameters. The follow-up date was 12 months after the fourth PRP treatment. Results: The mean age was 61.7 ± 15.3 years. The overall success rate was 50% with the post-treatment mean GRA of 1.5 ± 1.1. Complete dryness was achieved in 12 patients (46.2%) after the PRP treatment, and 7 (26.9%) kept total continence at 12 months. The mean VAS of SUI score decreased significantly from 6.4 ± 2.3 to 3.9 ± 2.3 after treatment (p < 0.001). The abdominal leak point pressure increased significantly from 117.5 ± 63.8 to 133.6 ± 61.7 cmH2O (p = 0.045). No perioperative adverse events or severe complications occurred, except 1 (3.8%) patient reported straining to void which was self-limited. Conclusion: Repeated urethral sphincter injections of autologous PRP are a safe procedure that provides significant reduction in the severity of female SUI and a mid-term durability, suggesting PRP treatment is effective to increase urethral sphincter resistance for female SUI.

Modern radiographic imaging in multiple myeloma, what is the minimum requirement?

Imaging innovations offer useful techniques applicable to many oncology specialties. Treatment advances in the field of multiple myeloma (MM) have increased the need for accurate diagnosis, particularly in the bone marrow, which is an essential component in myeloma-defining criteria. Modern imaging identifies osteolytic lesions, distinguishes solitary plasmacytoma from MM, and evaluates the presence of extramedullary disease. Furthermore, imaging is increasingly valuable in post-treatment response assessment. Detection of minimal residual disease after therapy carries prognostic implications and influences subsequent treatment planning.Whole-body low-dose Computed Tomography is now recommended over the conventional skeletal survey, and more sophisticated functional imaging methods, such as 18F-Fluorodeoxyglucose Positron Emission Tomography , and diffusion-weighted Magnetic Resonance Imaging are proving effective in the assessment and monitoring of MM disease. This review focuses on understanding indications and advantages of these imaging modalities for diagnosing and managing myeloma.

Magnetic Resonance Imaging in the Contemporary Management of Medulloblastoma: Current and Emerging Applications.

Medulloblastoma, the most common malignant primary brain tumor in children, is now considered to comprise of four distinct molecular subgroups-wingless (WNT), sonic hedgehog (SHH), Group 3, and Group 4 medulloblastoma, each associated with distinct developmental origins, unique transcriptional profiles, diverse phenotypes, and variable clinical behavior. Due to its exquisite anatomic resolution, multiparametric nature, and ability to image the entire craniospinal axis, magnetic resonance imaging (MRI) is the preferred and recommended first-line imaging modality for suspected brain tumors including medulloblastoma. Preoperative MRI can reliably differentiate medulloblastoma from other common childhood posterior fossa masses such as ependymoma, pilocytic astrocytoma, and brainstem glioma. On T1-weighted images, medulloblastoma is generally iso- to hypointense, while on T2-weighted images, the densely packed cellular component of the tumor is significantly hypointense and displays restricted diffusion on diffusion-weighted imaging. Following intravenous gadolinium, medulloblastoma shows significant but variable and heterogeneous contrast enhancement. Given the propensity of neuraxial spread in medulloblastoma, sagittal fat-suppressed T1-postcontrast spinal MRI is recommended to rule out leptomeningeal metastases for accurate staging. Following neurosurgical excision, postoperative MRI done within 24-48h confirms the extent of resection, accurately quantifying residual tumor burden imperative for risk assignment. Post-treatment MRI is needed to assess response and effectiveness of adjuvant radiotherapy and systemic chemotherapy. After completion of planned therapy, surveillance MRI is recommended periodically on follow-up for early detection of recurrence for timely institution of salvage therapy, as well as for monitoring treatment-related late complications. Recent studies suggest that preoperative MRI can reliably identify SHH and Group 4 medulloblastoma but has suboptimal predictive accuracy for WNT and Group 3 tumors. In this review, we focus on the role of MRI in the diagnosis, staging, and quantifying residual disease; post-treatment response assessment; and periodic surveillance, and provide a brief summary on radiogenomics in the contemporary management of medulloblastoma.

Nanatinostat (Nstat) and Valganciclovir (VGCV) in Relapsed/Refractory (R/R) Epstein-Barr Virus-Positive (EBV +) Lymphomas: Final Results from the Phase 1b/2 VT3996-201 Study

Nanatinostat (Nstat) and Valganciclovir (VGCV) in Relapsed/Refractory (R/R) Epstein-Barr Virus-Positive (EBV +) Lymphomas: Final Results from the Phase 1b/2 VT3996-201 Study

Improvement in the Assessment of Response to Preoperative Chemoradiotherapy for Rectal Cancer Using Magnetic Resonance Imaging and a Multigene Biomarker.

Simple SummaryPreoperative chemoradiotherapy is now the gold standard for treating locally advanced rectal cancer and has been demonstrated to decrease local recurrence and promote sphincter preservation. Therefore, developing methods to accurately predict patients’ response to chemoradiation is imperative for choosing the best surgical option after chemoradiation and predicting the oncologic outcomes of patients. Radiological tools and endoscopy are the most commonly used tools for post-treatment response assessment. In addition, examining the expression levels of genes correlated with treatment response could provide clinicians with more power to gauge each patient’s potential to respond. In this study, we explored how biological and radiological tools can be used together to provide a more tailored and multidimensional representation of patients’ response status.The response to preoperative chemoradiotherapy (PCRT) is correlated with oncologic outcomes in patients with locally advanced rectal cancer. Accurate prediction of PCRT response before surgery can provide crucial information to aid clinicians in further treatment planning. This study aimed to develop an evaluation tool incorporating a genetic biomarker and magnetic resonance imaging (MRI) to improve the assessment of response in post-CRT patients with locally advanced rectal cancer. A total of 198 patients who underwent PCRT followed by surgical resection for locally advanced rectal cancer between 2010 and 2016 were included in this study. Each patient’s response prediction index (RPI) score, a multigene biomarker developed in our previous study, and magnetic resonance tumor regression grade (mrTRG) score were added to create a new predictive value for pathologic response after PCRT, called the combined radiation prediction value (cRPV). Based on the new value, 121 and 77 patients were predicted to be good and poor responders, respectively, showing significantly different cRPV values (p = 0.001). With an overall predictive accuracy of 84.8%, cRPV was superior to mrTRG and RPI for the prediction of pathologic chemoradiotherapy response (mrTRG, 69.2%; RPI, 77.3%). In multivariate analysis, cRPV was found to be the sole predictor of tumor response (odds ratio, 32.211; 95% confidence interval, 14.408–72.011; p = 0.001). With its good predictive value for final pathologic regression, cRPV may be a valuable tool for assessing the response to PCRT before surgery.

Head and neck imaging surveillance strategy for HPV-positive oropharyngeal carcinoma following definitive (chemo)radiotherapy

PurposeTo describe the utilization pattern of head and neck (HN) surveillance imaging and explore the optimal strategy for radiologic “residual” lymph node (LN) surveillance following definitive (chemo)radiotherapy (RT/CRT) in human papillomavirus (HPV)+ oropharyngeal carcinoma (OPC). MethodsAll HPV+ OPC patients who completed RT/CRT from 2012 to 2015 were included. Schedule and rationale for post-treatment HN-CT/MRI were recorded. Imaging findings and oncologic outcomes were evaluated. ResultsA total of 1036 scans in 412 patients were reviewed: 414 scans for first post-treatment response assessment and 622 scans for the following reasons: follow-up of radiologic “residual” LN(s) (293 scans/175 patients); local symptoms (227/146); other (17/16); unknown (85/66). Rate of scans with “unstated” reason varied significantly among clinicians (3–28%, p < 0.001) and none of them yielded any positive imaging findings. First post-treatment scans identified 192 (47%) patients with radiologic “residual” LNs. Neck dissection (ND) was performed in 28 patients: 16 immediately (6/16 positive), 10 after one follow-up scan (2/10 positive), and 2 after 2nd follow-up scan (1/2 positive). Thirty patients had >2 consecutive follow-up scans at 2–3-month intervals, and none showed subsequent imaging progression or regional failure. ConclusionsPattern of HN imaging utilization for surveillance varied significantly among clinicians. Imaging surveillance reduces the need for ND. However, routine HN-CT/MR surveillance without clinical symptoms/signs does not demonstrate proven value in identifying locoregional failure or toxicity. Radiologic “residual” LNs without adverse features are common. If two subsequent follow-up scans demonstrate stable/regressing radiologic “residual” LNs, clinical surveillance without further imaging appears to be safe in this population.

Investigational CD47-Blocker TTI-622 Shows Single-Agent Activity in Patients with Advanced Relapsed or Refractory Lymphoma: Update from the Ongoing First-in-Human Dose Escalation Study

Investigational CD47-Blocker TTI-622 Shows Single-Agent Activity in Patients with Advanced Relapsed or Refractory Lymphoma: Update from the Ongoing First-in-Human Dose Escalation Study

Response Assessment with 18F-FDG PET/CT Scan in Patients with Anal Cancer Treated with Radical Radiotherapy

Functional imaging like positron emission tomography (PET) in combination with computed tomography (CT) has been found to be an important tool in post-treatment response assessment in several malignancies. The objective of this study was to identify the utility of early post-treatment response assessment with 18F-FDG PET/CT scan in patients with squamous cell carcinoma (SCC) of anal canal primarily treated with radical radiotherapy. We reviewed the provincial population database for anal cancer patients who were treated with radical radiotherapy (2005-2015) and subsequently underwent post-treatment 18F-FDG PET/CT scans (majority within 12-17 weeks after treatment completion) for response assessment. Information related to patient and tumor characteristics, treatment regimen were collected. Disease free survival (DFS) and cancer specific survival (CSS) were estimated using Kaplan-Meier product limit method. Cox multivariable proportional hazard model was used to determine the association of post-treatment maximum standardized uptake value (SUVmax) as a continuous variable with DFS and CSS after adjustment for age at diagnosis, stage, radiotherapy dose, use of concomitant chemotherapy, use of salvage surgery, sex and performance status. A total of 287 patients were treated with radical radiotherapy over the time period of the study and 56 had post-treatment response assessment with PET/CT. Median age of the study cohort was 60.5 years (IQR, 53-66 years). Median radiotherapy dose was 54 Gy (IQR, 53.6-54 Gy). Among a total of 56 patients, concurrent chemotherapy was offered in 53 (95%) patients. Mean post-treatment SUVmax for the primary tumor and node were 2.6(±3.9) and 4.3(±6.7). On multivariable analysis (MVA), post-treatment SUVmax for the primary tumor had a significant association with CSS (hazard ratio (HR): 1.39, 95% confidence interval (CI): 1.13-1.70, p=0.002). The HR for post-treatment nodal SUVmax was 1.09 (95% CI: 0.88-1.36, p=0.4). The association of post-treatment SUVmax of tumor (HR: 1.01, 95% CI: 0.86-1.18, p=0.88) or node (HR: 1.10, 95% CI: 0.92-1.31, p=0.31) with DFS was not statistically significant. The current population-based study shows significant correlation of presence of FDG avid residual tumor with cancer specific survival. Every 1 unit increase in post-treatment SUVmax of the primary tumor was associated with 39% increase in the relative risk of death. Although post-treatment residual FDG avid node showed similar direction of association, the overall association was not statistically significant which could be attributed to the limited sample size. The study alludes to the importance of post-treatment PET based response assessment in patients with anal SCC and early institution of salvage treatment in presence of FDG avid residual tumor to avoid potentially fatal consequences. Further prospective validation with randomized clinical trial is worthwhile to prove this hypothesis.

Evaluation of Post-Stereotactic Body Radiation Therapy Response Assessment for Hepatocellular Carcinoma: An Appraisal of RECIST, m-RECIST and WHO Criteria

Response Evaluation Criteria in Solid Tumors (RECIST) is a validated criterion to evaluate response to liver directed therapy in hepatocellular carcinoma (HCC); however, RECIST criteria are inadequate for assessing early response to Stereotactic Body Radiotherapy (SBRT). In this analysis, we evaluated post-treatment response assessment using RECIST, modified-RECIST and World Health Organization (WHO) criteria in patients receiving SBRT for HCC. This retrospective analysis included HCC patients treated with SBRT at two institutions between 2009 and 2016. Included patients had pathologically proven or met radiologic criteria for the diagnosis of HCC and received SBRT. Additionally, only patients with a multiphase contrast liver MR or CT imaging scan in the 6 weeks prior to SBRT and at least one follow-up MR/CT 1-6 months post-SBRT were included in this analysis. For each lesion treated with SBRT, the maximum two diameters, the maximum bidimensional enhancement diameter, the product of the bidimensional diameters and the product of bidimensional enhancement diameters were measured. From these parameters, post-SBRT response was assessed according to RECIST 1.1, mRECIST, and WHO criteria. Fifty-six lesions in 45 patients (32 M, 13 F; mean age: 66.7 ± 7.6 years) were included in this analysis. Twenty-five of these lesions were previously treated with liver-directed therapies. Sixteen lesions were followed with CT and 40 with MR. 14 of the 56 (25%) treated lesions were isointense to the surrounding liver parenchyma in the arterial phase on at least one follow-up examination. Hyperenhancement of the adjacent liver parenchyma was observed for several months post-SBRT. For two lesions previously treated non-SBRT, the SBRT target was a residual tumor at the periphery of the original lesion; in post-SBRT images of these lesions, it was similarly impossible to distinguish between residual tumor and hyperenhancing normal liver parenchyma. The post-SBRT liver parenchymal enhancement limited standard therapeutic response assessment. For RECIST 1.1 and WHO criteria, the lesion diameter evaluation was limited in 1 lesion and pseudoprogression was seen in 2 lesions; with mRECIST criteria, the lesion viability evaluation was limited by isointensity in the arterial phase to the surrounding liver parenchyma in 23 examinations (0-6 months follow-up: 12 exams; 7-12 months follow-up: 7 exams; 13-24 months: 4 exams) and pseudoprogression was seen in 4 lesions. Liver parenchymal changes induced by SBRT may limit post-treatment assessment using current response assessment criteria, especially during early follow-up examinations. New criteria should be evaluated to assess post-SBRT treatment response.

Improvements in Imaging of Hodgkin Lymphoma: Positron Emission Tomography.

18-Fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (FDG PET/CT) is currently the criterion standard of lymphoma imaging and recommended through all stages of Hodgkin lymphoma management. Accurate staging is important for risk stratification and initial choice of therapy and also for the planning of postchemoradiotherapy. 18-Fluoro-2-deoxy-D-glucose PET/CT frequently leads to upstaging and potentially a more intensive treatment. Visual-only assessment of staging and interim scans is being accompanied by quantitative and semiquantitative methods to measure metabolic tumor volume, total lesion glycolysis, and so on. It is still unclear if these methods significantly improve the value of FDG PET/CT by visual assessment only. Because of the good prognostic value of FDG PET/CT, a large number of studies have used interim FDG PET to tailor treatment to the individual patients, according to their early metabolic response rather than according to their pretreatment prognostic features. 18-Fluoro-2-deoxy-D-glucose PET/CT is standard of care for posttreatment response assessment but has no place in routine follow-up of Hodgkin lymphoma patients in remission.

Stereotactic Body Radiation Therapy for Early-Stage Non-Small Cell Lung Cancer: A Primer for Radiologists.

The past 2 decades have seen a rapid growth in use of stereotactic body radiation therapy (SBRT) for the management of non-small cell lung cancer (NSCLC). Not only is SBRT the reference standard for treatment of early-stage node-negative NSCLC in medically inoperable patients, it is also currently challenging the role of surgery for early-stage operable disease. SBRT is also used to treat recurrent disease and has a role in the management of multiple synchronous lung cancers. Imaging changes after SBRT differ from the changes after conventional radiation therapy in many ways, the knowledge of which is pertinent for accurate image interpretation. Posttreatment response assessment and detection of recurrent disease are heavily reliant on radiologic assessment, and often the decision to treat recurrent disease is based on the imaging findings themselves. This article provides a comprehensive review of the concepts of SBRT and the current indications for its use in the treatment of early-stage NSCLC, as well as a discussion of the CT findings seen after SBRT compared with the changes after conventional radiation therapy. Radiologic findings that are suggestive of recurrent disease and the imaging pitfalls are also highlighted. Finally, the rare complications after SBRT are described. SBRT is a major component of the changing treatment paradigms for early- and late-stage NSCLC. The imaging findings after SBRT often determine the next steps in a patient's clinical management. Therefore, radiologists must be familiar with the uses of this therapy and its radiologic appearance to be able to effectively contribute to the care of patients with NSCLC. ©RSNA, 2018.

Staging and following common pediatric malignancies: MRI versus CT versus functional imaging.

Most pediatric malignancies require some form of cross-sectional imaging, either for staging or response assessment. The majority of these are solid tumors and this review addresses the role of MRI, as well as other cross-sectional and functional imaging techniques, for evaluating the most common pediatric solid tumors. The primary emphasis is on neuroblastoma, hepatoblastoma and Wilms tumor, three of the most common non-central-nervous-system (CNS) pediatric solid tumors encountered in young children. The initial focus will be a review of the imaging techniques and approaches used for diagnosis, staging and early post-treatment response assessment, followed by a discussion of the role surveillance imaging plays in pediatric oncology and a brief review of other emerging imaging techniques. The lessons learned here can be applied to most other pediatric tumors, including rhabdomyosarcoma, Ewing sarcoma and osteosarcoma, as well as germ cell tumors, neurofibromatosis and other rare tumors. Although lymphoma, in particular Hodgkin lymphoma, represents one of the more common pediatric malignancies, this is not discussed in detail here. Rather, many of the lessons that we have learned from lymphoma, specifically with regard to how we integrate both anatomical imaging and functional imaging techniques, is applied to the discussion of the other pediatric solid tumors.