PSMA PET/CT to evaluate response to SBRT for prostate cancer bone metastases

Background: In the current study we evaluated 68Ga PSMA PET/ CT to measure local control of bone metastasis in oligometastatic prostate cancer patients treated with SBRT.  Materials and methods: After the institutional review board approval, a retrospective review of medical records of consecutive prostate cancer patients treated between 2014 and 2018 was conducted. Only medical records of patients that were treated with SBRT for bone metastasis and had pre-and post-SBRT 68Ga PSMA PET/CT scans were included in our study. Data extracted from the medical files included patient-related (age), disease-related (Gleason score, site of metastasis), and treatment-related factors and outcomes. Results: During the study period, a total of 12 patients (15 lesions) were included, with a median age of 73 years. The median follow-up was 26.5 months (range 13–45 months). Median time of 68Ga PSMA PET/ CT follow up was 17.0 months (range 3–39 months). The median pre-treatment PSA was 2 ng/mL (range 0.56–44 ng/mL) vs. post treatment PSA nadir of 0.01 ng/mL (0.01–4.32) with a median time to nadir of 7 months (range, 2–12). Local control was 93% during the follow up period and there was correlation with PSMA avidity on PET. None patients developed recurrences in the treated bone. None of the patients had grade 3 or more toxicities during follow-up. Conclusions: SBRT is a highly effective and safe method for treatment of prostate cancer bone metastases. More studies are required to determine if SBRT provides greater clinical benefit than standard fractionation for oligometastatic prostate cancer patients. 68Ga PSMA PET/CT should be further investigated for delineation and follow-up

Hairy cell leukemia presenting as multiple discrete hepatic lesions

The involvement of hairy cell leukemia in the liver is in the form of portal and sinusoidal cellular infiltration. Here we describe the first case of hepatic hairy cell leukemia presenting as multiple discrete lesions, which was treated successfully. We suggest that in the investigation of discrete hepatic lesions in cases of cancer of unknown primary, hairy cell leukemia should be considered. The excellent response of hairy cell leukemia to therapy highlights the need for such a consideration

68Ga-PSMA PET/CT in prostate cancer patients – patterns of disease, benign findings and pitfalls

Abstract Background 68Ga-PSMA PET/CT has an important role in assessment of prostate cancer patients with biochemical recurrence and is evolving in staging high- and intermediate risk disease. The aim of present study was to describe the metastatic patterns and frequency of involved sites of prostate cancer and to assess the incidence of benign Ga68-PSMA avid PET/CT findings in a large patient population. Methods 68Ga-PSMA PET/CT studies performed in two tertiary medical centers over a period of 24 months were retrospectively reviewed. The incidence and location of pathological 68Ga-PSMA avid foci, suspicious to represent malignancy, as well as those of unexpected benign foci of increased 68Ga-PSMA activity were documented and analyzed. Results There were 445 68Ga-PSMA studies in 438 men (mean age 72.4, range 51–92 years) with prostate cancer referred for biochemical failure (n = 270, 61%), staging high-risk disease (n = 112, 25%), response assessment (n = 30, 7%), follow-up (n = 22, 5%) and suspected bone metastases (n = 11, 2%). 68Ga-PSMA avid disease sites were observed in 319 studies (72%), in 181 studies (67%) for biochemical recurrence, 94 studies for staging (84%) (p < 0.05), in 22 studies for response assessment (73%), 10 follow up studies (45%) and in five patients with suspected bone metastases (45%). 68Ga-PSMA avid lesions were most commonly detected in the prostate (n = 193, 43%), loco-regional spread (n = 51, 11%), abdomino-pelvic nodes (n = 129, 29%) and distant metastases (n = 158, 36%), including bone metastases (n = 11, 25%), distant lymphadenopathy (n = 29, 7%) and other organs (n = 18, 4%). Distant 68Ga-PSMA-avid metastases were commonly seen in patients with biochemical recurrence (14/21 lesions), but were not seen in patient referred for staging (p < 0.013). There were 96 non-malignant 68Ga-PSMA avid foci in 81 studies, most common in reactive lymph nodes (n = 36, 38%), nonmalignant bone lesions (n = 21, 22%), thyroid nodules (n = 9, 9%), ganglions (n = 9, 9%) and lung findings (n = 8, 8%). Conclusion The distribution of 68Ga-PSMA avid metastatic lesions is similar to data previously reported mainly from autopsy with comparable detection rates, indicating 68Ga-PSMA PET/CT is an accurate detection tool in patients with metastatic prostate cancer. If confirmed by further prospective studies 68Ga-PSMA PET/CT should be included in the guidelines to evaluate disease extent in these patients

The Utility of 68Ga-PSMA PET/CT in Decisions Regarding Administering Salvage Radiotherapy to Men with Prostate Cancer

Background: Numerous papers have described 68Ga-prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT)&rsquo;s sensitivity in identifying prostate cancer (PCa) recurrence. This study aimed to characterize the role of 68Ga-PSMA PET/CT in deciding to re-irradiate pelvic structures. Methods: 68Ga-PSMA PET/CT scans performed at Sheba Medical Center over seven years in 113 men were reviewed. All had undergone radiation to the prostate (70, 61.9%) or post-radical prostatectomy radiation to the prostate fossa (PF) (43, 48.1%), and had local or oligometastatic PCa recurrence and received salvage radiotherapy (SRT) based on PET/CT findings. Results: Mean age was 70.7 years. The mean grade group was 2.9; the mean prostate-specific antigen was 9.0. The 68Ga-PSMA PET/CT positive findings included: 37 (32.7%) in the prostate, 23 (20.4%) in seminal vesicles, 7 (6.2%) in the PF, and 3 (2.7%) in the seminal vesicle fossa. The mean standardized uptake value was 10.6 &plusmn; 10.2 (range: 1.4&ndash;61.6); the mean lesion size was 1.8 &plusmn; 3.5 mm (range: 0.5&ndash;5.1). SRT was directed toward the prostate and seminal vesicles in 48 (42.5%), PF in 18 (15.9%), and intrapelvic lymph node and bone in 47 (41.6%). Toxicities were mostly mild to moderate. Conclusion: 68Ga-PSMA PET/CT-identified relapse with targeted SRT was well-tolerated and may result in less onerous treatments

Response to Anti-PD1/L1 Antibodies in Advanced Urothelial Cancer in the ‘Real-Life’ Setting

Immune checkpoint inhibitors (ICIs) are now the standard of care for metastatic urothelial carcinoma (mUC) patients. Our aim was to describe the activity of ICIs in mUC and find the clinical parameters associated with response. This is a retrospective, single-center chart review of mUC patients receiving ICIs. The overall survival (OS) was plotted using the Kaplan–Meier method and was compared using a log-rank test. Associations between the variables and responses were analyzed by univariate and multivariable analyses, using either logistic regression or a Chi-square/Fisher’s exact test. Ninety-four patients received ICIs, 85% of which were in the second line or beyond; the median age was 71.8 years, and 82% were men. Six (6.4%), 11 (11.7%), 7 (7.4%) and 70 (74.5%) patients achieved a complete response (CR), partial response (PR), mixed response/stable disease (M/SD) or progressive disease (PD), respectively. The median overall survival was 3.2 months for the entire cohort and was significantly different according to the response pattern—not reached, 32.3, 6.4 and 2.0 months for CR, PR, M/SD and PD, respectively. The response was not significantly associated with the line of treatment. ‘Site of metastasis’ was associated with the response, and the absolute neutrophil count was borderline associated with the response. In summary, we found a substantial variance in the potential benefit from ICIs in mUC, emphasizing the need for predictive biomarkers and frequent monitoring of mUC patients receiving ICIs

Clinical Variables Associated with PSA Response to Lutetium-177-PSMA ([177Lu]-PSMA-617) Radionuclide Treatment in Men with Metastatic Castration-Resistant Prostate Cancer

Lutetium-177-PSMA ([177Lu]-PSMA-617), a radiolabeled small molecule, binds with high affinity to prostate-specific membrane antigen (PSMA), enabling targeted radiation therapy to metastatic prostate lesions. Our objective was to retrospectively analyze the activity of [177Lu]-PSMA-617 given off-trial to men with metastatic castration resistant prostate cancer (mCRPC) and identify clinical factors associated with PSA response. Electronic medical records of all men treated with [177Lu]-PSMA-617 were reviewed and analyzed. Overall survival was calculated using the Kaplan&ndash;Meier method. The association between potential variables and PSA response was analyzed by univariate analysis, using either logistic regression or &chi;2/Fisher&rsquo;s exact test. Multivariable analysis was carried out using logistic regression on all categorical variables with a P-value of &lt;0.1 on univariate analysis. Variables found to be statistically significant were then used to define a categorical score. A total of 52 patients received at least one cycle of [177Lu]-PSMA-617. Clinical benefit was observed in 28 patients (52%). PSA decline &ge;20% and &ge;50% was observed in 26 (50%) and 18 patients (35%), respectively. Achievement of any PSA decline at first measurement was significantly associated with survival. There was a negative association between the number of previous chemotherapy lines and PSA decline above 20%. Univariate analysis followed by multivariable analysis showed that older age and higher hemoglobin were significantly associated with a PSA decline &gt;20%. A score combining these two parameters was significantly associated with PSA response. In summary, [177Lu]-PSMA-617 is active in the &lsquo;real-life&rsquo; setting of heavily pretreated men with mCRPC

Reexpansion of atelectasis caused by use of continuous positive airway pressure (CPAP) before radiation therapy (RT)

Introduction: Although radiation therapy (RT) is an effective treatment for malignant atelectasis, its accurate delivery is challenging because of difficulty differentiating between tumor and atelectatic lung. Furthermore, reexpansion of lung during treatment repositions tumor and normal structures necessitating replanning to ensure treatment accuracy. Facilitating lung reexpansion before initiation of RT may improve RT treatment accuracy, spare normal tissue, and reduce obstructive symptoms. We report a case of reexpansion of right upper lobe (RUL) atelectasis caused by use of continuous positive airway pressure (CPAP) before RT. Case report: A 52-year-old woman presented with dyspnea and cough. Imaging studies showed an RUL mass with atelectasis. Bronchoscopy showed extrinsic compression of the RUL and middle lobe bronchi. Biopsy showed small cell lung cancer. Staging with positron emission tomography-computed tomography (CT) and contrast enhanced CT of brain showed no other disease. Following 4 cycles of platinum-based chemotherapy, CT imaging showed a decrease in tumor volume, but persistent RUL atelectasis. She agreed to participate in an institutional study to evaluate the use of CPAP to reduce respiratory motion and immobilize tumors during RT. During CPAP training, she complained of vertigo, headache, and weakness and refused simulation. The next day she reported less dyspnea and completed training and CT simulation without difficulty. CT simulation with CPAP showed reexpansion of the RUL. Lung volume increased from 2170 to 3767 mL (74 %). Gross tumor volume, clinical volume, and planning volume decreased 46%, 45%, and 38%, respectively. Mean lung dose and mean heart dose decreased 20% and 51%, respectively. CPAP was used daily for 1 hour before and during treatment. Cone beam CT scans showed that the RUL remained inflated throughout treatment. Conclusion: This is the first reported use of CPAP for reexpansion of atelectasis before RT planning and treatment. Reexpansion of atelectasis improved RT planning, decreased dose to uninvolved lung, and removed the need for replanning. Further study of CPAP as an initial intervention to improve RT delivery in patients with malignant atelectasis is warranted

Secukinumab Loss of Efficacy Is Perfectly Counteracted by the Introduction of Combination Therapy (Rescue Therapy): Data from a Multicenter Real-Life Study in a Cohort of Italian Psoriatic Patients That Avoided Secukinumab Switching

Since psoriasis (PsO) is a chronic inflammatory disease, patients may experience a drug failure also with very effective drugs (i.e., secukinumab) and, consequently, dermatologists have two therapeutic options: switching or perform a combination therapy (rescue therapy) to save the drug that had decreased its efficacy. At the moment no studies focused on combination/rescue therapy of secukinumab, so we performed a 52-weeks multicenter retrospective observational study that involved 40 subjects with plaque psoriasis that experienced a secondary failure and were treated with combination therapy (ciclosporin (n = 11), MTX (n = 15), NB-UVB (n = 7) and apremilast (n = 7)). After 16 weeks of rescue/combination therapy, PASI and a DLQI varied respectively from 8 [7.0&ndash;9.0] and 13 [12.0&ndash;15.0], to 3 [2.8&ndash;4.0] and 3 [2.0&ndash;3.3]), suggesting a significant improvement of daily functionality and quality of life. Results were maintained at 52 weeks. No side effects were experienced during the study. Secukinumab remains a safety and effective drug for PsO patients also in the IL-23 and JAK inhibitors era. The rescue therapy is a valid therapeutic option in case of secukinumab secondary failure

Very Low Prostate PET/CT PSMA Uptake May Be Misleading in Staging Radical Prostatectomy Candidates

Purpose: to evaluate a unique subpopulation of radical prostatectomy (RP) candidates with &ldquo;negative&rdquo; prostate 68Ga-labeled prostate-specific membrane antigen (PSMA) positron emission tomography (PET) computed tomography (CT) imaging scans and to characterize the clinical implications of misleading findings. Materials and Methods: This case-control retrospective study compared the final histological outcomes of patients with &ldquo;negative&rdquo; pre-RP PSMA PET/CT prostate scans (with a prostate maximal standardized uptake value [SUVmax] below the physiologic uptake) to those with an &ldquo;intense&rdquo; prostatic tracer uptake (with a SUVmax above the physiologic uptake). The patients underwent an RP between March 2015 and July 2019 in five academic centers. Data on the demographics, comorbidities, prostate-specific antigen (PSA) and rectal exam findings, prior biopsies, imaging results, biopsies, and RP histology results were collected. Results: Ninety-seven of the 392 patients who underwent an RP had PSMA PET/CT imaging preoperatively. Fifty-two (54%) had a &ldquo;negative&rdquo; uptake (in the study group), and 45 (46%) had a &ldquo;positive&rdquo; uptake (in the control group). Only the lesion size and SUVmax values on the PSMA PET/CT differed between the groups preoperatively. On the histological analysis, only the ISUP score, seminal vesicles invasion, T stage, and positive margin rates differed between the groups (p &lt; 0.05), while 50 (96%) study group patients harbored clinically significant disease (ISUP &ge; 2), with an extra-prostatic disease in 24 (46%), perineural invasion in 35 (67%), and positive lymph nodes in 4 (8%). Conclusions: Disease aggressiveness generally correlated with an intense PSMA uptake on the preoperative PSMA PET/CT, but a subpopulation of patients with clinically significant cancer and aggressive characteristics showed a deceptively weak PSMA uptake. These data raise a concern about the unqualified application of PSMA PET/CT for staging RP candidates