Cyclin-dependent kinase 4/6 inhibitors in the treatment of advanced or metastatic breast cancer.

OBJECTIVE: Despite the relatively high cure rates in early-stage breast cancer, advanced and metastatic breast cancer cases are associated with more inauspicious patient outcomes. Fortunately, with the advent of cyclin-dependent kinase (CDK)4/6 inhibitors (e.g. palbociclib, ribociclib, and abemaciclib) with endocrine therapy, survival in advanced and metastatic breast cancer has appreciably improved. In the current review, we discuss these distinctions and the concomitant implications associated with the individual CDK4/6 inhibitors. DATA SOURCES: We conducted an extensive PubMed search comprising several review articles on the topic of advanced or metastatic breast cancer treatment, with specific terms that included CDK4/6 inhibitors, treatment, and breast cancer. DATA SUMMARY: Palbociclib, ribociclib, and abemaciclib have exhibited superior progression-free survival differences compared to endocrine therapy alone. However, there are differences among the various CDK4/6 inhibitors with regard to overall survival, tolerability and quality of life. CONCLUSIONS: Ribociclib may be indicated for pre/perimenopausal patients, whereas abemaciclib is potentially recommended to address endocrine-resistant or visceral disease. Alternatively, palbociclib is associated with lower discontinuation rates than abemaciclib and unlike ribociclib, QTc prolongation is not observed with palbociclib.

Current analysis of the survival implications for minimally invasive surgery in the treatment of early-stage cervix cancer.

Early-stage cervical cancer (ESCC) is managed with radical hysterectomy, a procedure that can be performed either via open surgery or minimally invasive surgery (MIS), the latter of which is accomplished via traditional laparoscopy or robotic-assisted surgery. Previously, MIS was routinely incorporated into the management of ESCC due to the approach's reduced operative morbidity and truncated hospital stay duration, but more recent clinical evidence has since impugned the efficacy of MIS because of the reportedly inferior disease-free survival and overall survival outcomes compared to open surgery. However, additional studies have documented equivalent outcomes among the various surgical modalities, suggesting further exploration of clinical factors as we endeavor to conclusively determine the standard of care for patients diagnosed with ESCC.

Prolonged endocrine therapy in the management of hormone receptor-positive early-stage breast cancer: What is the appropriate duration?

AIM: The clinical benefits associated with 5 years of endocrine therapy in the treatment of hormone receptor-positive, early-stage breast cancer (ESBC) have been well-substantiated. However, numerous studies have reported on the results of extended (i.e., >5 years) endocrine therapy to further effectuate a clinical benefit, with varying outcomes. Hence, the purpose of this study is to review these prolonged investigations and endeavor to clarify their corresponding treatment implications. METHODS: We reviewed the study findings from several randomized controlled trials and meta-analyses, which incorporated clinical outcomes from pre-and postmenopausal, hormone receptor-positive, ESBC patients. RESULTS: Hormone receptor-positive, ESBC patients treated with 5 years of endocrine therapy, who are node-negative with tumors <2 cm, will unlikely benefit from five additional years of treatment. Conversely, in women with larger tumors and node-positive disease, 7-8 total years of endocrine therapy may be indicated. Ultimately, clinicians should also consider the attendant side effects from endocrine therapy, namely bone fractures, namely cardiovascular symptoms, and vasomotor symptoms, when considering the appropriate treatment regimen. CONCLUSIONS: While increased duration of endocrine therapy may selectively accord significant clinical benefits, prior to determining the patient's treatment interval, physicians should also assess the cumulative side effects from endocrine therapy when endeavoring to maintain treatment compliance and bolster quality of life.

A phase II, open-label, non-randomized, prospective study assessing paclitaxel, carboplatin and metformin in the treatment of advanced stage ovarian carcinoma.

OBJECTIVE: The purpose of this study was to assess the efficacy and tolerability of a paclitaxel, carboplatin and metformin regimen in the first-line treatment of advanced-stage ovarian, fallopian tube, and primary peritoneal carcinoma. METHODS: Eligible subjects underwent surgery and 6 cycles of neoadjuvant or adjuvant dose-dense intravenous paclitaxel (80 mg/m²), carboplatin (area under the curve 5 or 6 on Day 1), and oral metformin (850 mg daily). Study participants who completed their primary therapy and attained a clinically defined complete or partial response (PR) were treated with a planned 12 cycles of paclitaxel (135 mg/m² every 21 days) and metformin (850 mg twice daily) maintenance therapy. RESULTS: Thirty subjects received a median of 6 cycles (range, 5-6) of primary induction chemotherapy and were eligible for response evaluation; twenty-three patients exhibited a complete response, while 3 study patients obtained a PR (an overall response rate of 86.7%). Grade 3-4 hematological toxicity included neutropenia (43.3%), thrombocytopenia (10%) and anemia (36.7%). There was no incidence of grade 3-4 neuropathy although 15 patients (50%) developed grade ≤2 neurotoxicity. Additionally, we observed grade ≤2 diarrhea in 20 (66.7%) subjects. The median progression-free survival was 21 months (range, 3-52) and overall median survival was 35 months (range, 15-61). The subjects also received an aggregate 103 cycles (median, 12; range, 6-12) of maintenance chemotherapy. CONCLUSION: The study results suggest that the combination of paclitaxel, carboplatin and metformin is associated with moderate efficacy and a reasonable toxicity profile.

Hormone Therapy and Risk of Breast Cancer: Where Are We Now?

Several studies have examined the clinical benefits of hormone replacement therapy (HRT). However, because long-term use of HRT has been implicated as a risk factor for the development of breast cancer, some women remain skeptical when considering this therapy to address their vasomotor symptoms. Hence, physicians and nurses should actively engage in constructive discourse with their patients regarding HRT while specifically reviewing the potential risks of its extended use as well as provide the available medical alternatives the patients could potentially use.

Robotic-Assisted Surgery for the Treatment of Breast and Cervical Cancers.

Background: Robotic-assisted surgery facilitates the performance of numerous, complex procedures, namely conferring precision, flexibility, and control that is otherwise unavailable with conventional laparoscopy; and compared to open surgery, robotic-assisted surgery is ostensibly associated with fewer complications, reduced intraoperative complications, and shorter hospital stay duration. Nevertheless, the American College of Obstetricians and Gynecologists and the Food and Drug Administration have criticized the pervasive acceptance of robotic-assisted surgery, given the absence of randomized clinical trial data compared to traditional laparoscopy and open procedures, not to mention the increased surgical cost. Conclusions: While the research data continue to be borne out, surgeons should exercise considerable discretion in selecting the surgical approach from which their patients would derive the greatest clinical benefit.

Talc powder and ovarian cancer: what is the evidence?

Talc is a desiccant that has been historically used as baby powder by numerous women to enhance their feminine hygiene. Talc has been identified in proximity to asbestos; accordingly, retrospective and case-control studies have implicated the role of talc use in the development of ovarian cancer, whereas prospective evaluations have not documented concordant findings. Moreover, the positive associations derived from case-control studies have been remote and the putative causal factors remain inconclusive. Consequently, one should be circumspect regarding the assertion that genital talc powder application induces ovarian cancer development.

A Rare Case of Idiopathic Pyometra in a Premenopausal Patient.

Pyometra is a very uncommon disease principally occurring in postmenopausal women. It is characterized by the accumulation of purulent material within the uterine cavity. This paper presents the clinical history of a 35-year-old premenopausal woman with otherwise normal menstruation who developed heavy menstruation and was diagnosed with a benign pyometra of indeterminate etiology in March 2017. The patient underwent repeated ultrasound-guided drainage, dilation and curettage, and antibiotic therapy. Biopsies of the pelvic sidewall revealed endometriosis in June 2017. The heavy menstruation and suppurative fluid in the uterus of the patient persisted in which intramuscular leuprolide acetate was prescribed to address the endometriosis and heavy menstrual bleeding. Ultimately, the leuprolide acetate effectively resolved the patient's bleeding and pyometra. The medication was concluded after 12 months of supervision and the patient is currently symptom free. Pyometra is an unusual condition rarely identified in premenopausal women. Drainage and antibiotic therapy are routinely employed; however, one may consider gonadotropin-releasing hormone agonist medication to potentially confer a beneficial patient outcome in rare cases where endometriosis and bleeding are intractable.

A retrospective study comparing the efficacy of dose-dense chemotherapy, intraperitoneal chemotherapy and dose-dense chemotherapy with hyperthermic intraperitoneal chemotherapy in the treatment of advanced stage ovarian carcinoma.

OBJECTIVES: Hyperthermic intraperitoneal chemotherapy (HIPEC), intraperitoneal chemotherapy (IP) and dose-dense (DD) chemotherapy have been employed with varying success in the treatment of advanced stage ovarian carcinoma. Despite the clinical benefits associated with these specific forms of chemotherapy administration, they have not been comparatively analyzed, vis-à-vis their efficacy. STUDY DESIGN: Advanced stage ovarian cancer patients who were treated with platinum/taxane chemotherapy via a DD regimen (n = 100), IP approach (n = 81) or a DD regimen in conjunction with HIPEC (n = 64) were retrospectively evaluated. The clinical variables of interest were patient age, body mass index, surgery and pathology data, chemotherapy regimen, inclusion of maintenance therapy, and progression free/overall survival. RESULTS: Progression free survival (PFS) was significantly more pronounced in the HIPEC (34.9 months) and IP (34.0 months) patients, compared to the DD group (27.6 months) (P = 0.005). A cox-proportional hazards regression model indicated that there was a decreased risk of disease progression accorded to the patients who were treated with IP chemo or HIPEC and DD chemotherapy (HR, 0.43; 95 % CI: 0.21-0.88; P = 0.022) and the subjects who underwent optimal cytoreductive surgery (HR, 2.42; 95 % CI: 1.22-4.80; P = 0.011). Positive BRCA status (HR, 0.434; 95 % CI: 1.59-3.44; P = 0.001) and number of chemotherapy regimens (HR, 1.36; 95 % CI: 1.159-1.61; P = 0.001) were significantly correlated with improved OS although we did not discern a survival benefit associated with any of the chemotherapy treatments (P = 0.136). CONCLUSION: We observed PFS advantages conferred to the ovarian cancer patients treated with HIPEC and IP chemotherapy compared to DD chemotherapy. However, an overall survival advantage related to the chemotherapy regimens was not borne out, possibly due to the retrospective nature of the study or differing time periods wherein the specific patient cohorts underwent treatment.

Pronounced clinical response following the oncolytic vaccinia virus GL-ONC1 and chemotherapy in a heavily pretreated ovarian cancer patient.

Heavily pretreated ovarian cancer patients become progressively chemoresistant, and thereafter, only scant treatments potentially accord reasonable, albeit limited clinical efficacy. We describe a case involving a 67-year-old ovarian cancer patient who underwent multiple lines of chemotherapy and presented with recurrent disease and a CA-125 of 4112 U/mL. Thenceforth, she was treated with GL-ONC1 oncolytic viral therapy that was administered laparoscopically in accordance with a clinical trial. The patient subsequently received chemotherapy and during the fourth cycle, her CA-125 decreased to 99 U/mL; moreover, a computed tomography scan of the pelvis exhibited significant disease reduction. Viral therapy hypothetically confers significant promise in the treatment of recurrent ovarian cancer, especially in patients who remain unresponsive to traditional medications.

Cranial and intra-axial metastasis originating from a primary ovarian Dysgerminoma.

Dysgerminomas are aggressive germ cell tumors that typically have a favorable prognosis, especially in patients diagnosed with early stage disease. We recount the history of a 23-year-old woman who was treated for a stage IA ovarian dysgerminoma in November 2017. Postoperatively, the patient was noncompliant insofar as obtaining routine lab evaluations; ten months later, she was diagnosed with a cranial metastasis that extended into the meninges. The patient subsequently underwent a posterior fossa craniotomy and adjuvant etoposide, bleomycin and cisplatin chemotherapy to which she initially responded; however, during cycle 4, she developed pancytopenia whereupon the chemotherapy was summarily discontinued. Thereafter, the patient was surveilled and currently, she remains in clinical remission. Early stage ovarian dysgerminoma, albeit rarely, has the capacity to metastasize to the cranium or brain, further underscoring the significance of employing active follow-up with these patients.

The Management of a patient with a fragmented intrauterine device embedded within the cervical canal.

A 28-year-old woman presented with a malpositioned intrauterine device (IUD) that was fragmented and significantly entrenched within the cervical canal and myometrium. IUD malposition with concomitant device fragmentation and embedded segments, albeit rare, should be a consideration given the device's prevalence.

Dramatic clinical response following dabrafenib and trametinib therapy in a heavily pretreated low grade serous ovarian carcinoma patient with a BRAF V600E mutation.

Low grade serous ovarian cancer (LGSOC) is a slowly growing, relatively chemoresistant neoplasm that is associated with a more favorable prognosis, especially compared to the disease's high-grade serous counterpart. We recount a case involving a 47-year-old, heavily pretreated LGSOC patient who presented with an elevated CA-125 of 1047 U/mL during her recent course of pemetrexed therapy. Thereafter, she underwent molecular profiling, which revealed a BRAF V600E mutation; accordingly, the patient was administered dabrafenib and trametinib combination therapy, a regimen that resulted in a precipitous decline of her CA-125 to 35 U/mL following the 6th cycle. The patient's favorable response to BRAF and MEK 1/2 inhibitor therapy underscores the significance of molecular profile testing and the use of targeted therapy regardless of tissue origin, especially in cases for whom standard management is limited or ineffective.

Clear cell carcinoma of the pelvic side wall arising from endometriosis.

Endometriosis is a condition wherein an ectopic layer of endometrial tissue arises in an extra-uterine location, often effecting significant pelvic pain and infertility. While very uncommon, there have been reported cases of endometriosis undergoing malignant transformation, frequently involving the ovaries and seldom in extra-gonadal regions. We recount a case depicting a 63 year-old woman who presented with an apparent inguinal hernia in 2017; she was ultimately diagnosed with a pelvic side wall clear cell carcinoma and attendant metastatic disease to the medial groin, which emanated from endometriosis. Malignant transformation of endometriosis identified in the pelvic side wall is a very rare finding. Nevertheless, oncologists should maintain a high index of suspicion in patients with a history of endometriosis or pelvic surgery.

The incidence of occult malignancy following uterine morcellation: A ten-year single institution experience retrospective cohort study.

INTRODUCTION: When the Food and Drug Administration (FDA) initially reported on the parlous incidence (0.28%) of occult malignancy identified following uterine power morcellation, investigations thereafter documented their particular experience with this surgical procedure. Nevertheless, the precise risk of identifying a sarcoma following uterine morcellation remains indeterminate, primarily due to varying study patient risk factors, diagnostic criteria and operative approach. METHOD: We retrospectively evaluated subjects who underwent an endoscopic hysterectomy and uterine power morcellation for the treatment of a presumptive, benign indication from January 2006 until December 2015. The primary outcome was the incidence of an occult malignancy. Secondarily, we were interested in characterizing the patients' specific clinical (age, menopausal status, body mass index (BMI)) risk factors within the context of a confirmed malignant or pre-malignant pathology. RESULTS: We identified 281 patients who underwent endoscopic surgery that incorporated uterine morcellation. During the study period, one subject was ultimately diagnosed with a uterine leiomyosarcoma; the overall incidence of occult malignancy was 0.36%. There were also 3 cases of uterine premalignant disease on final pathology (2 patients had complex hyperplasia with or without atypia and 1 subject was diagnosed with a smooth muscle tumor of uncertain malignant potential (an incidence of 1.1%)). We were unable to establish any relationship between patient age, uterine weight, menopausal status or BMI and the incidence of a malignant or pre-malignant pathology (P > 0.05). CONCLUSION: The rate of occult malignancy in the present investigation was similar to previously documented studies and that which has been reported by the FDA. Additional study of methods in which to enhance preoperative work-up and mitigate the surgical risk for tumor cell dissemination is warranted.

The safety and feasibility of minimally invasive sentinel lymph node staging using indocyanine green in the management of endometrial cancer.

OBJECTIVES: The purpose of this study was to report on the feasibility of laparoscopic sentinel lymph node (SLN) staging using indocyanine green (ICG) in the management of endometrial cancer. STUDY DESIGN: We retrospectively evaluated the charts of presumed, clinical stage I endometrial cancer patients who underwent robotic-assisted surgery that incorporated mapping with ICG and SLN dissection from January 2016 until February 2017. Patient demographics, operative characteristics (e.g., complications, lymph node counts) and pathology data were evaluated. RESULTS: There were 87 patients who were included in the study. A total of 370 lymph nodes were removed, of which 245 were SLNs; unilateral and bilateral mapping of the SLNs was achieved in 84 (96.5%) and 71 (81.6%) of subjects, respectively. There were 10 (11.5%) patients who had metastatic disease identified within 22 (5.9%) of the total (n = 370) lymph nodes extracted, 19 (7.7%) of which were sentinel lymph nodes. We did not observe any intraoperative complications. CONCLUSION: The results from our study suggest that minimally invasive SLN staging using ICG is a feasible procedure that is potentially effective at detecting metastases, which may ultimately attenuate the incidence of surgical morbidity.

The Impact of an Enhanced Recovery After Surgery Program on Patients Treated for Gynecologic Cancer in the Community Hospital Setting.

OBJECTIVES: The purpose of this study was to compare the outcomes of gynecologic oncology patients treated in the community hospital setting either under the auspices of an enhanced recovery after surgery (ERAS) protocol or in accordance with physician discretion. METHODS: We retrospectively evaluated a series of consecutive gynecologic oncology patients who were managed via open surgery in coincident with an ERAS pathway from January 2015 to December 2016. They were compared with a historical open surgery cohort who was treated from November 2013 to December 2014. The primary clinical end points encompassed hospital length of stay, hospital costs, and patient readmission rates. RESULTS: There were 86 subjects accrued in the ERAS group and 91 patients in the historical cohort. The implementation of ERAS occasioned a greater than 3-day mean reduction in hospital stay (8.04 days for the historical group vs 4.88 days for the ERAS subjects; P = 0.001) and correspondingly diminished hospital costs ($11,877.47/patient vs $9305.26/patient; P = 0.04). Moreover, there were 2 readmissions (2.3%) in the ERAS group compared with 4 (4.4%) in the historical cohort (P = 0.282). CONCLUSIONS: The results from our investigation suggest that adhering to an ERAS protocol confers beneficial hospital length of stay and hospital cost outcomes, without compromising patient readmission rates. Additional investigation scrutinizing the impact of ERAS enactment with more defined study variables in a larger, randomized setting is warranted.