Faculty Bibliography

Objective: The use of medical marijuana (MM) in cancer patients was legalized in New York state in 2016. Reported benefits of MM include reduction of cancer-associated pain, nausea, vomiting, fatigue, and improved appetite, as well as mitigating other side effects of cancer treatment. Tetrahydrocannabinol (THC) and cannabidiol (CBD), both components of MM, have been shown to have therapeutic benefit for cancer-related symptoms. Dosing of MM is described in terms of the THC:CBD ratio. While the general therapeutic benefits have been documented, there is a paucity of data on MM use in patients with gynecologic cancers (GC). We sought to evaluate the effect of medical marijuana for symptom management in patients with GC at our institution.
Method(s): We retrospectively identified women with GC using MM between May 2016 and August 2018 from the medical record. Demographic data, cancer diagnosis, dosage form, quantity, frequency, length of treatment, indication, and reported efficacy of MM were collected.
Result(s): We identified 34 patients using MM for a diagnosis of GC. Table 1 lists the patient characteristics and indications for MM and dosing. Median age of patients using MM was 60 years (46-78 years). Median length of treatment with MM was 189 days (11-761 days). Response to MM included 17(50%) improvement in symptoms; 3 (9%) minimal change; 10 (29%) not reported yet; and 4 (12%) unknown. Overall, among patients for whom symptom improvement was available to date, 17/20 (85%) noted improvement. Four (12%) patients reported unwanted side effects, which were euphoria, dizziness, fatigue, and paranoia. Three patients who reported side effects received MM with a 1:1 THC:CBD ratio; the other patient received a low THC:high CBD dosing. Only one (3%) patient ceased medical marijuana use because of untoward adverse effects. All the patients who reported an improvement in symptoms while using MM were concurrently receiving chemotherapy. Improvement in symptoms was not related to formulation, form, or length of treatment of MM.
Conclusion(s): An improvement in symptoms associated with cancer and treatment was noted in over 80% of GC patients using MM, and very few reported adverse side effects. MM is likely to be a promising treatment for pain, nausea, and anorexia in GC patients and should be considered in the armamentarium of palliative cancer treatment options. [Figure presented]
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Objective: TSR-042 is an investigational humanized antiprogrammed death (PD)-1 monoclonal antibody that binds with high affinity to the PD-1 receptor and effectively blocks interaction with the ligands PD-L1 and PD-L2. TSR-042 is being evaluated in patients with advanced solid tumors in the ongoing phase I/II GARNET trial (NCT02715284) (Sachdev JC et al. Ann Oncol. 2017(suppl 5):28:420;1185P). Here we present safety and efficacy data from the previously treated recurrent or advanced endometrial cancer (EC) cohorts, along with pharmacokinetics (PK) and receptor occupancy (RO) findings at the recommended phase II dose (RP2D).
Method(s): Patients with previously treated recurrent or advanced EC were evaluated. Patients received the RP2D of TSR-042: 500 mg Q3 weeks for the first 4 cycles and 1,000 mg Q6 weeks thereafter. Antitumor activity was assessed by investigators per immune related (ir) RECIST. Serum and peripheral blood mononuclear cells were collected for PK and RO measurements, respectively.
Result(s): A total of 110 EC patients received at least 1 dose of TSR-042 at the RP2D. The median age was 66.0 years. The median number of prior lines of therapy for advanced or metastatic disease was 1 (range 0-3). Overall, 94 patients had at least 1 tumor assessment (n = 79) or discontinued treatment prior to week 12 (n = 15); the overall response rate (including confirmed and unconfirmed responses per irRECIST) among these patients was 27.7% (50.0% in microsatellite instability-high [MSI-H] patients; 19.1% in microsatellite stable [MSS] patients). The disease control rate among these patients was 48.9%. At the time of data cutoff, responses were ongoing in 88.4% of responders. Detailed efficacy results based on microsatellite status will be presented at the meeting. Sixty-eight EC patients (61.8%) had at least 1 treatment-related adverse event (TRAE). Grade >=3 TRAEs were reported in 13 patients (11.8%), and the most common grade >=3 TRAE was aspartate aminotransferase increased (2.7%). TSR-042 PK was linear and dose-proportional. Maximal RO was observed at the RP2D consistent with previous results and was maintained through the course of treatment.
Conclusion(s): TSR-042 demonstrated robust clinical activity in patients with previously treated recurrent or advanced EC in both MSI-H and MSS subgroups and a safety profile similar to approved anti-PD-1 therapies.
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High-grade serous ovarian cancer (HGSOC) is hallmarked by early onset of peritoneal dissemination, which distinguishes it from low-grade serous ovarian cancer (LGSOC). Here, we describe the aggressive nature of HGSOC ascitic tumor cells (ATCs) characterized by integrin α5^high (ITGA5^high) ATCs, which are prone to forming heterotypic spheroids with fibroblasts. We term these aggregates as metastatic units (MUs) in HGSOC for their advantageous metastatic capacity and active involvement in early peritoneal dissemination. Intriguingly, fibroblasts inside MUs support ATC survival and guide their peritoneal invasion before becoming essential components of the tumor stroma in newly formed metastases. Cancer-associated fibroblasts (CAFs) recruit ITGA5^high ATCs to form MUs, which further sustain ATC ITGA5 expression by EGF secretion. Notably, LGSOC is largely devoid of CAFs and the resultant MUs, which might explain its metastatic delay. These findings identify a specialized MU architecture that amplifies the tumor-stroma interaction and promotes transcoelomic metastasis in HGSOC, providing the basis for stromal fibroblast-oriented interventions in hampering OC peritoneal propagation.

Brachytherapy is well-established as an integral component in the standard of care for treatment of patients receiving primary radiotherapy for cervical cancer. A decline in brachytherapy has been associated with negative impacts on survival in the era of modern EBRT techniques. Conformal external beam therapies such intensity modulated radiation therapy (IMRT) or stereotactic body radiation therapy (SBRT) should not be used as alternatives to brachytherapy in patients undergoing primary curative-intent radiation therapy for cervical cancer. Computed tomography or magnetic resonance image-guided adaptive brachytherapy is evolving as the preferred brachytherapy method. With careful care coordination EBRT and brachytherapy can be successfully delivered at different treatment centers without compromising treatment time and outcome in areas where access to brachytherapy maybe limited.

BACKGROUND:A minimally invasive surgical approach has proven to decrease peri- and post-operative complications and shorten duration of hospital stay, however there is limited data evaluating the safety of robotic-assisted surgery and early hospital discharge in the elderly population. As age is a well-known, independent risk factor for peri-operative morbidity and gynecologists treat many elderly patients, this is an important area of study. OBJECTIVE:To evaluate discharge timing and surgical outcomes in elderly compared to younger patients undergoing robotic-assisted gynecologic surgery. STUDY DESIGN/METHODS:Retrospective cohort study of all patients who underwent robotic-assisted gynecologic surgery at a high volume, single institution from January 2013 - May 2016. Demographic information, discharge timing, and peri- and post-operative outcomes were compared for patients <65 years to those >65 years using univariate and multivariate analyses. RESULTS:), (28 vs. 26, P<0.001) and American Society of Anesthesia (ASA) classification (P<0.001). Elderly were more likely to have malignancy as the indication for surgery (68% vs. 11%, P<0.001) and to undergo hysterectomy (81% vs. 38%, P<0.001) or surgery with lymph node dissection (44.5% vs. 7.1%, P<0.001). Elderly patients had higher incidence of intra-operative complications (9% vs. 4.6%, P=0.002) and longer median hospital stay (17 vs. 7 hours, P<0.001) compared to younger patients. Same day discharge was more common in younger patients (76% vs. 45%, P<0.001) and elderly patients were more likely to have admissions lasting >23 hours (13% vs. 3%, P<0.001) on univariate and multivariate analysis. Analysis of post-operative outcomes included 2,023 patients with available post-operative data (80% of total population) (1,794 <65y, 229 > 65y). There were no differences between elderly and younger patients in overall post-operative complications, reoperations, intensive care unit admissions, emergency room visits, or hospital readmission within six weeks of surgery. CONCLUSIONS:Despite having more pre-operative risk factors and more surgically complex procedures, elderly patients undergoing robotic-assisted gynecologic surgery had similar post-operative complication rates and almost half of elderly patients were safely discharged the day of surgery. Our data suggest that robotic-assisted gynecologic surgery and early hospital discharge are safe in elderly patients.

Brachytherapy is well-established as an integral component in the standard of care for treatment of patients receiving primary radiotherapy for cervical cancer. A decline in brachytherapy has been associated with negative impacts on survival in the era of modern EBRT techniques. Conformal external beam therapies such intensity modulated radiation therapy (IMRT) or stereotactic body radiation therapy (SBRT) should not be used as alternatives to brachytherapy in patients undergoing primary curative-intent radiation therapy for cervical cancer. Computed tomography or magnetic resonance image-guided adaptive brachytherapy is evolving as the preferred brachytherapy method. With careful care coordination EBRT and brachytherapy can be successfully delivered at different treatment centers without compromising treatment time and outcome in areas where access to brachytherapy maybe limited.

We describe a case of the first successful treatment of platinum refractory clear cell ovarian cancer with secondary cytoreductive surgery and placement of Calypso transponders to facilitate post-operative volumetric arc radiation therapy. In the setting of both primary and recurrent disease, patients with clear cell ovarian cancer are less responsive to standard chemotherapy and those treated with radiation therapy may have improved outcomes compared to the use of other treatment modalities. Volumetric arc radiation therapy with implantable transponders is feasible, and allows for the targeted treatment of sites of metastatic disease while limiting toxicity to surrounding structures and can be considered for patients with recurrent ovarian cancer and oligometastatic disease.