Stergios Boussios

The Impact of Systemic Therapy Beyond First-line Treatment for Advanced Cervical Cancer

AIMS Despite recent advances in the primary and secondary prevention of cervical cancer, a significant number of women present with or develop metastatic disease. There is currently no consensus on the standard of care for second-line systemic treatment of recurrent/metastatic cervical cancer. The purpose of this study was to evaluate the second-line systemic therapy used and the associated outcomes in a single cancer centre. MATERIALS AND METHODS A retrospective review of patients with cervical cancer who received one or more lines of treatment for recurrent or metastatic cervical cancer at the Royal Marsden Hospital between 2004 and 2014 was carried out. The primary objective was to establish the types of second-line systemic treatment used. Secondary end points included objective response rate, progression-free survival and overall survival after second-line therapy. RESULTS In total, 75 patients were included in the study; 53 patients (70.7%) received second-line therapy for recurrent/metastatic disease. The most common second-line therapy was weekly paclitaxel (28.3%). Carboplatin-based chemotherapy (24.5%), targeted agent monotherapy within clinical trials (22.6%), docetaxel-based chemotherapy (13.2%), topotecan (9.4%) and gemcitabine (1.9%) were also used. The objective response rate to second-line therapy was 13.2%, which included three partial responses to carboplatin and paclitaxel, two partial responses to docetaxel-based chemotherapy, one partial response to weekly paclitaxel and one partial response to cediranib. Twenty-two patients (41.5%) achieved stable disease at 4 months. The median progression-free survival for women treated with second-line therapy was 3.2 months (95% confidence interval 2.1-4.3) and median overall survival was 9.3 months (95% confidence interval 6.4-12.5). Thirty-nine per cent of patients received third-line therapy. CONCLUSION Seventy per cent of patients treated with first-line systemic therapy for recurrent/metastatic cervical cancer subsequently received second-line treatment but response rates were poor. There remains no standard of care for second-line systemic therapy for advanced cervical cancer. Patients should be considered for clinical trials whenever feasible, including novel targeted agents and immunotherapy.

Cancer specific risk in multiple sclerosis patients

Multiple sclerosis (MS) is a chronic central nervous system (CNS) autoimmune disease. Studies of cancer risk in MS patients have shown inconsistent findings. A pubmed search of the literature on cancer risk in patients with MS was conducted and found published relative studies. The majority of these studies concluded that there was overall either reduced or no increased risk of developing malignancies between patients with MS compared to the general population. However, several studies suggested that patients with MS may have reduced risk in specific cancers such as of the digestive and respiratory organs, prostate, ovary, or increased risk in breast, brain and bladder tumors. At present it is uncertain if the immunologic profile of MS patients may be related to the increased or reduced frequency of some cancers and warrants further investigation.

Current and future biomarkers in colorectal cancer

Colorectal cancer (CRC), one of the leading causes of death among cancer patients, is a heterogeneous disease and is characterized by diversions in multiple molecular pathways throughout its evolutionary process. To date, specific mutations in RAS and RAF genes are tested in everyday clinical practice along with mismatch repair gene deficiency, serving either as prognostic or predictive biomarkers, providing information for patient risk stratification and the choice of appropriate therapy. However, ongoing studies are focusing on the potential role of recently discovered genetic and epigenetic alterations in the management of CRC patients and their potential prognostic or predictive value. To overcome the problem of tumor heterogeneity as well as the practical obstacles of access to tumor tissue, and to achieve real-time monitoring of disease and therapy efficacy, liquid biopsies constitute a novel technology worth exploring. CRC screening and management is entering a new era where molecular testing will be applied to genomic material extracted from easily accessible bodily fluids.

Primary Pulmonary Malignant Melanoma: Report of an Important Entity and Literature Review

Malignant melanoma involving the respiratory tract is nearly always metastatic in origin, and primary tumors are extremely rare. Published data on primary pulmonary malignant melanomas are limited. Up to now 40 relevant cases have been reported in the English literature. Herein, we report a case of a 56-year-old female patient who presented with intracranial metastases due to primary pulmonary melanoma. She underwent bronchoscopy and died 5 months after the initial diagnosis despite the administered biochemotherapy and subsequent immunotherapy. To establish the diagnosis of primary pulmonary malignant melanoma, any extrapulmonary origin was excluded by detailed examination and radiographic imaging. Moreover, an extensive review of the literature regarding this rare entity has been performed.

A review on pregnancy complicated by ovarian epithelial and non-epithelial malignant tumors: Diagnostic and therapeutic perspectives

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Dynamics of Neutrophils-to-Lymphocyte Ratio Predict Outcomes of PD-1/PD-L1 Blockade

Introduction Baseline neutrophil-to-lymphocyte ratio (NLR) has been repeatedly reported as a significant prognostic factor in advanced cancer patients. We explored whether changes in NLR may predict outcome of advanced cancer patients enrolled into phase 1 trials and treated with PD-1/PD-L1 inhibitors. Patients and Methods Advanced cancer patients enrolled into phase 1 trials between September 2013 and May 2016 and treated with anti-PD-1/PD-L1 agents were included in this retrospective study. NLR was calculated at baseline and after 2 cycles of treatment. Royal Marsden Hospital (RMH) prognostic score and Eastern Cooperative Group (ECOG) performance status (PS) were determined at baseline. Kaplan-Meier estimation and Cox regression analyses were used to assess the impact of NLR dynamics on PFS. Results Among the 55 patients eligible, 26 (47%) were treated with anti-PD-L1 monotherapy, 22 (40%) received single agent anti-PD-1, and 7 (13%) were given a tyrosine kinase inhibitor (TKI) plus a PD-1 inhibitor. Neither ECOG PS nor RMH prognostic score was significantly associated with PFS in our cohort, whereas changes in NLR significantly impacted on PFS. Conclusion Changes in the NLR may be a useful predicting factor in advanced cancer patients treated with anti-PD-1/PD-L1 agents. Further prospective trials are needed to verify these findings.

Metastatic Spinal Cord Compression: Unraveling the Diagnostic and Therapeutic Challenges

Malignant spinal cord compression (MSCC) is one of the most devastating complications of cancer. Patients often present with a history of progressive pain, paralysis, sensory loss, progressive spinal deformity, and loss of sphincter control. It is an emergency that requires rapid decision making on the part of several specialists, given the risk of permanent spinal cord injury or death. The goals of treatment in spinal metastases are pain control and improvement of neurological function in order to achieve better quality of life (QoL). The standard of care in most cases is rapid initiation of corticosteroids in combination with either surgical decompression in case of an operable candidate, followed by radiation therapy (RT) or RT alone. Surgery is associated with improved outcomes, but is not appropriate for many patients presenting with advanced symptoms of MSCC, such as paralysis, or those with a poor performance status, or cachexic state, as well as altered mental conditions, co-morbidities, surgical risks, and limited life expectancy. On the other hand, aggressive surgical treatment and post-operative RT is advocated for those with more favorable prognosis, or who are expected to have higher neurological recovery potential. Many candidates may require for combined anterior and posterior approaches to effectively deal with the compressive pathology and stabilize the spine. Most patients are presently treated by primary RT, given with the aim of improving function and symptom management. However, there is still debate regarding the most appropriate RT schedule. Rehabilitation can serve to relieve symptoms, QoL, enhance functional independence, and prevent further complications. Ambulatory status has been found to be an important prognostic factor for patients with MSCC.

Spinal Ewing Sarcoma Debuting with Cord Compression: Have We Discovered the Thread of Ariadne?

Ewings sarcoma (ES) of the spine with cord or radicular compression as an initial sign is infrequent. It is unclear, in alleviating a neurological deficit, whether decompressive laminectomy is preferred over chemotherapy. Herein, a literature review of the treatment approaches to the primary or metastatic ES of the spine has been performed. Collected data included clinical features of the patients, treatment, and outcome. There are reported 69 cases with initial presentation of cord or radicular compression of spinal cord, arising from primary or metastatic ES, treated either with initial chemotherapy and/or radiotherapy (RT) (33.33%, n=23), or decompressive surgery (66.66%, n=46). The median age at diagnosis was 17.95 years old (range=0.06-60), and 38 patients (55.07%) were male. Eighteen (78.26%) were initially treated with chemotherapy combined with RT, whereas 3 (13.04%) were managed with RT alone. One patient (4.35%) received only corticosteroids, while there are not available data for the treatment of another one (4.35%). The remaining 46 patients (66.66%) were initially treated with decompressive surgery. Among them, 40 (57.97%) received postoperative chemotherapy, RT or combined modality therapy, whereas 6 patients (8.69%) were not treated adjuvantly. Sixteen out of 23 patients (69.6%) treated with systemic therapy, and 37 from 46 (80.43%) of those managed with decompressive laminectomy were still alive at a mean follow-up period of 2.11 years (range=0.16-6) and 3.45 years (range=0.16-26.08), respectively. To summarize, spinal resection and reconstruction followed by adjuvant treatment reduce the risk of local recurrence, and improve long-term survival. However, ES of the spine is not a distinct clinical entity and can be either managed with chemotherapy and/or RT, similarly to other localization.

Malignant peritoneal mesothelioma: clinical aspects, and therapeutic perspectives

Malignant peritoneal mesothelioma (MPM) is a rare disease with a wide clinical spectrum. It arises from the peritoneal lining and commonly presents with diffuse, extensive spread throughout the abdomen and, more rarely, metastatic spread beyond the abdominal cavity. Computed tomography, magnetic resonance imaging and positron-emission tomography are important diagnostic tools used for the preoperative staging of MPM. The definitive diagnosis is based on histopathological analysis, mainly via immunohistochemistry. In this regard, paired-box gene 8 negativity represents a useful diagnostic biomarker for differentiating MPM from ovarian carcinoma. In addition, BRCA1-associated protein-1 (BAP1) loss is specific to MPM and allows it to be distinguished from both benign mesothelial lesions and ovarian serous tumors. Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) has become an increasingly important therapeutic approach, while systemic therapies are still being developed. Histology, Ki-67, completeness of cytoreduction, age, sex, and baseline thrombocytosis are commonly used to optimize patient selection for CRS with HIPEC. Additionally, it is well recognized that, compared to other subtypes, an epithelial morphology is associated with a favorable prognosis, whereas baseline thrombocytosis predicts an aggressive biologicalbehavior. Platelets and other immunologic cytokines have been evaluated as potential novel therapeutic targets. Epigenetic modifiers, including BAP1, SETD2 and DDX3X, are crucial in mesothelial tumorigenesis and provide opportunities for targeted treatment. Overexpression of the closely interacting phosphoinositide 3-kinase (PI3K) and the mammalian target of rapamycin (mTOR) pathways appears crucial in regulation of the malignant phenotype. The use of targeted therapies with PI3K-mTOR-based inhibitors requires further clinical assessment as a novel approach.

Managing Melanoma During Pregnancy

Cutaneous melanoma is one of the most frequently encountered malignancies in pregnant women. Still, the tendency to delay pregnancy to later reproductive age along with the age-dependent increase in the incidence of melanoma are likely to result in higher incidences of gestational melanoma in the next decades. As the diagnosis of melanoma in the course of pregnancy is not an exceptional situation, the provision of treatment raises certain issues that are at once medical, ethical, and philosophical. The management of gestational melanoma poses a significant challenge to surgeons, oncologists, and patients alike. Generalized guidelines may not be applicable or appropriate because of patient variability. In clinical practice, this translates into individualized patient management. In every case, the involvement of a multidisciplinary team with clinical and psychosocial expertise in melanoma therapy is essential.