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PURPOSEThe growing cancer burden in Botswana has been linked to aging, lifestyle factors, and high HIV infection prevalence. The government has designated four geographically distributed hospitals as public oncology centers (POCs). A needs assessment was undertaken to ascertain the characteristics of cancer care at these centers.METHODSA multisite cross-sectional survey study of cancer care was conducted with oncology staff at Princess Marina Hospital (PMH), Nyangabgwe Referral Hospital (NRH), Sekgoma Memorial Hospital (SMH), and Letsholathebe II Memorial Hospital (LMH) from February to April 2021. At each POC, a focal person (experienced nurse working in oncology) identified relevant oncology staff and confirmed service availability.RESULTSOnly PMH and NRH had a broad array of diagnostic, surgical, and treatment services. In addition, PMH was the only center with a a dedicated inpatient oncology service, a multidisciplinary committee to review patients, and a palliative care team. To support the only national cancer screening program, for cervical cancer, all POCs offered Pap tests. Mammography, available at PMH and NRH, was used solely for diagnosis. Patients from POCs requiring radiation therapy were referred to Gaborone Private Hospital at government expense. For perceived service availability, 51 staff, mainly oncologists, physicians, and nurses, were surveyed (66% based at PMH). Perceptions of services revealed a few concerns, for example, numerous staff considered hysterectomies for cervical cancer available when they were only performed at PMH.CONCLUSIONDespite Botswana's efforts to increase the proximity of cancer services to patients, there are marked gaps, particularly at the two district-level POCs, SMH and LMH. In the future, SMH and LMH could provide selected services for specific prevalent cancers on-site, as well as follow-up and palliative care.

Purpose: Emerging data suggest that metastasis-directed therapy (MDT) improves outcomes in patients with oligometastatic castration-sensitive prostate cancer (omCSPC). Prostate-specific membrane antigen positron emission tomography (PSMA-PET) can detect occult metastatic disease, and PSMA response has been proposed as a biomarker for treatment response. Herein, we identify and validate a PSMA-PET biomarker for metastasis-free survival (MFS) following MDT in omCSPC. Methods and Materials: We performed an international multi-institutional retrospective study of patients with omCSPC, defined as ≤3 lesions, treated with metastasis-directed stereotactic ablative radiation who underwent PSMA-PET/computed tomography (CT) before and after (median, 6.2 months; range, 2.4-10.9 months) treatment. Pre- and post-MDT PSMA-PET/CT maximum standardized uptake value (SUVmax) was measured for all lesions, and PSMA response was defined as the percent change in SUVmax of the least responsive lesion. PSMA response was both evaluated as a continuous variable and dichotomized into PSMA responders, with a complete/partial response (at least a 30% reduction in SUVmax), and PSMA nonresponders, with stable/progressive disease (less than a 30% reduction in SUVmax). PSMA response was correlated with conventional imaging-defined metastasis-free survival (MFS) via Kaplan-Meier and Cox regression analysis. Results: A total of 131 patients with 261 treated metastases were included in the analysis, with a median follow-up of 29 months (IQR, 18.5-41.3 months). After stereotactic ablative radiation, 70.2% of patients were classified as PSMA responders. Multivariable analysis demonstrated that PSMA response as a continuous variable was associated with a significantly worse MFS (hazard ratio = 1.003; 95% CI, 1.001-1.006; P = .016). Patients classified as PSMA responders were found to have a significantly improved median MFS of 39.9 versus 12 months (P = .001) compared with PSMA nonresponders. Our study is limited as it is a retrospective review of a heterogenous population. Conclusions: After stereotactic ablative radiation, PSMA-PET response appears to be a radiographic biomarker that correlates with MFS in omCSPC. This approach holds promise for guiding clinical management of omCSPC and should be validated in a prospective setting.

Chromophobe renal cell carcinoma (chRCC) is one of the less common types of kidney cancer and generally portends a more favorable prognosis. RCC with sarcomatoid differentiation has a more aggressive clinical course with poor outcomes. Four cases of chRCC with varying degrees of sarcomatoid differentiation were retrospectively reviewed at our institution, and clinicopathologic data as well as clinical courses were reported. Patients with higher degrees of sarcomatoid differentiation and larger tumors at presentation generally had and worse overall survival. chRCC with sarcomatoid differentiation portends a poor prognosis with limited data on systemic treatment options for metastatic disease.

Purpose: Approximately 7% of patients with newly diagnosed prostate cancer (PCa) in the US will have have metastatic disease. The dogma that there is no role for surgery in this population has been questioned recently. Here we report long-term outcomes of a phase 1 clinical trial on cytoreductive radical prostatectomy. Materials and methods: This is a multicenter phase 1 trial. The major inclusion criterion was biopsy proven N1M0 or NxM1a/b PCa. Primary end point was the Clavien-Dindo-based major complication rate. Secondary outcomes were biochemical progression and overall survival. RNA-seq correlative study was conducted in nine select cases as a pilot study. Results: Final accrual was 32 patients of which 25 and 7 were cNxM1 and cN1M0, respectively. With the median follow-up of 46 months (interquartile range 31.7 - 52.7 months), 25 out of the 32 patients (75%) were alive at the time of last contact. There were three disparate groups based on the oncologic outcome: favorable, intermediate, and poor. In seven men with favorable response, androgen deprivation therapy was switched to intermittent approach and five remain free of any evidence of disease after more than two years off all systemic therapy with the normalization of serum testosterone. Of these five patients, three had M1 disease. Long-term use of one pad or less per day was 80%. RNA-seq analysis revealed an enriched downregulation of tumor necrosis factor (TNF)-α signature in the favorable group. Conclusion: Overall long-term oncologic outcome of cytoreductive radical prostatectomy was significantly higher than historical results. Importantly, the combination of surgery with systemic therapy may result in a long durable response in a minority of men who present with metastatic PCa.

Cancer incidence is rising across sub-Saharan Africa (SSA), and is often characterized by late-stage presentation, early age of onset and poor survival. While a number of oncology drugs are now improving the length and quality of life for cancer patients in high-income countries, significant disparities in access to a range of oncology therapeutics exist for SSA. A number of challenges to drug access such as drug costs, lack of infrastructure and trained personnel must be urgently addressed to advance oncology therapies for SSA. We present a review of selected oncology drug therapies that are likely to benefit cancer patients with a focus on common malignancies in SSA. We collate available data from seminal clinical trials in high-income countries to highlight the potential for these therapeutics to improve cancer outcomes. In addition, we discuss the need to ensure access to drugs within the WHO Model List of Essential Medicines and highlight therapeutics that require consideration. Available and active oncology clinical trials in the region is tabulated, demonstrating the significant gaps in access to oncology drug trials across much of the region. We issue an urgent call to action to address drug access due to the predicted rise in cancer burden in the region in coming years.

Background: Preclinical and retrospective data suggest that cytoreductive radical prostatectomy may benefit a subset of men who present with metastatic prostate cancer (mPCa). Herein, we report the results of the first planned Phase 1 study on cytoreductive surgery. Methods: From four institutions, 36 patients consented to the study. However, four did not complete surgery because of rapid disease progression (n = 3) and another because of an intraoperatively discovered pericolonic abscess. Men with newly diagnosed clinical mPCa to lymph nodes or bones were eligible. The primary endpoint was the rate of major perioperative complications (Clavien-Dindo Grade 3 or higher) occurring within 90 days of surgery. Results: The mean age at surgery was 64.0 years. The 90-day overall complication rate was 31.2% (n = 10), of which two (6.25%) were considered major complications: one acute tubular necrosis requiring temporary dialysis and one death. In men with more than 6 months of follow-up, 67.9% had prostate specific antigen nadir ≤0.2 ng/mL, while one patient experienced a rapid rise in prostate specific antigen and another a widely disseminated disease that resulted in death 5 months after surgery. Altogether, these results demonstrate that cytoreductive radical prostatectomy is safe and surgically feasible in selected patients who present with mPCa . Yet, there may be a small subset of patients in whom surgery may cause a significant harm. Conclusion: Therefore, cytoreductive surgery in men with mPCa should be limited to clinical trials until robust data are available. Keywords: Cytoreduction, Clinical trial, Metastasis, Prostate cancer

Abstract Background In this era of precision medicine, the DNA damage response (DDR) pathway has been shown to be a viable target of intervention in metastatic castration-resistant prostate cancer (CRPC) as approximately one-third of CRPC patients harbor DDR pathway mutations. To determine whether DDR pathway is a potential therapeutic target in localized disease, we analyzed The Cancer Genome Atlas (TCGA) in the present study. Methods TCGA is a publically available cancer genome database that is sponsored by the United States National Cancer Institute. Total of 455 cases were available in the database at the time of this analysis. Results DDR pathway gene mutations or copy number alterations were present in 136 (29.9%) of the 455 cases. On a univariate analysis, DDR pathway status did not correlate with serum prostate specific antigen, tumor stage or grade. However, among patients with high-risk features post-operatively (pathologic stage ≥ T3, Gleason score ≥ 8, or PSA > 20 ng/ml), DDR pathway alteration was associated with a lower overall survival (p = 0.0291). Conclusions Collectively these results suggest that DDR pathway alterations may also be significant in localized prostate cancer and agents such as PARP inhibitors should be considered in patients with a high-risk disease.

Abstract Background ONC201 is a small molecule antagonist of DRD2, a G protein-coupled receptor overexpressed in several malignancies, that has prolonged antitumor efficacy and immunomodulatory properties in preclinical models. The first-in-human trial of ONC201 previously established a recommended phase II dose (RP2D) of 625 mg once every three weeks. Here, we report the results of a phase I study that evaluated the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of weekly ONC201. Methods Patients ≥ 18 years old with an advanced solid tumor refractory to standard treatment were enrolled. Dose escalation proceeded with a 3 + 3 design from 375 mg to 625 mg of ONC201. One cycle, also the dose-limiting toxicity (DLT) window, was 21 days. The primary endpoint was to determine the RP2D of weekly ONC201, which was confirmed in an 11-patient dose expansion cohort. Results Twenty patients were enrolled: three at 375 mg and 17 at 625 mg of ONC201. The RP2D was defined as 625 mg with no DLT, treatment discontinuation, or dose modifications due to drug-related toxicity. PK profiles were consistent with every-three-week dosing and similar between the first and fourth dose. Serum prolactin and caspase-cleaved cytokeratin-18 induction were detected, along with intratumoral integrated stress response activation and infiltration of granzyme B+ Natural Killer cells. Induction of immune cytokines and effectors was higher in patients who received ONC201 once weekly versus once every three weeks. Stable disease of > 6 months was observed in several prostate and endometrial cancer patients. Conclusions Weekly, oral ONC201 is well-tolerated and results in enhanced immunostimulatory activity that warrants further investigation. Trial registration NCT02250781 (Oral ONC201 in Treating Patients With Advanced Solid Tumors), NCT02324621 (Continuation of Oral ONC201 in Treating Patients With Advanced Solid Tumors).

Prostate adenocarcinoma, the most common cancer in males in the United States, is often diagnosed in the nonmetastatic setting. The prognosis with metastatic prostate cancer is less favorable, though treatment options are typically effective in controlling the disease for an extended period. Hormonal therapy is the backbone to the management of prostate cancer metastases, decreasing the level of the prostate-specific antigen and reducing the patient's cancer-related symptoms. Pulmonary metastases, a relatively uncommon initial site of disease involvement, are expected to respond in a similar fashion to hormonal therapy as other organ or bone involvement. This report describes a patient with a newly diagnosed metastatic prostate cancer and a dramatic mixed response to hormonal therapy. This case should remind clinicians that pulmonary disease from prostate cancer may be an early metastatic finding, and can potentially progress even in the setting of an otherwise appropriate response to treatment.

Bilateral cryptorchidism is a rare occurrence and seminoma is the most common germ cell tumor found in undescended testes when they occur. We present the case of a patient with bilateral cryptorchidism who presented to our trauma center after a motor vehicle collision and was found incidentally to have a 17-cm intra-abdominal mass. The mass was subsequently biopsied and proven to be seminoma. The patient completed three cycles of bleomycin/etoposide/cisplatin chemotherapy and successfully underwent a postchemo retroperitoneal lymph node dissection with no viable residual tumor or positive lymph nodes found in the surgical specimen. He also had an orchiopexy of the contralateral testicle. The patient recovered fully and has been found to be recurrence-free four months postoperatively. We highlight the importance of cisplatin-based chemotherapy and extensive tumor resection as the mainstay of initial cancer control.

Background Bevacizumab and irinotecan may represent one of the most active treatments in progressive malignant glioma. Limited published experience with bevacizumab in patients with CNS tumors raises concerns regarding toxicity, particularly in regards to hemorrhage and thromboembolism. Methods We retrospectively reviewed 36 patients with progressive malignant glioma after prior resection, chemotherapy and radiation who were treated with bevacizumab at our institution. Patients were evaluated for bevacizumab-related adverse events, time to treatment failure (TTF) and overall survival (OS). Two patients who progressed or died prior to completion of 4 cycles of therapy were analyzed for adverse events only. Results Patients were treated with bevacizumab alone (1), bevacizumab plus irinotecan (31), or bevacizumab plus carboplatin (4). In 34 patients who received >4 cycles of bevacizumab, median TTF and OS were 16 and 32 weeks, respectively. Toxicities included 1 arterial thrombosis, 4 venous thromboses, and 3 clinically significant CNS hemorrhages. Conclusion Overall, our results confirm the efficacy and safety of bevacizumab in combination with chemotherapy in patients with progressive malignant glioma. Although the TTF and OS were less than previously reported with the combination of bevacizumab and irinotecan, this was an unselected patient population with 50% of patients having received >1 prior chemotherapy regimen.