Effectiveness of Carboplatin and Paclitaxel as First- and Second-Line Treatment in 61 Patients with Metastatic Melanoma

BACKGROUND: Patients with metastatic melanoma have a very unfavorable prognosis with few therapeutic options. Based on previous promising experiences within a clinical trial involving carboplatin and paclitaxel a series of advanced metastatic melanoma patients were treated with this combination. METHODS: Data of all patients with cutaneous metastatic melanoma treated with carboplatin and paclitaxel (CP) at our institution between October 2005 and December 2007 were retrospectively evaluated. For all patients a once-every-3-weeks dose-intensified regimen was used. Overall and progression free survival were calculated using the method of Kaplan and Meier. Tumour response was evaluated according to RECIST criteria. RESULTS: 61 patients with cutaneous metastatic melanoma were treated with CP. 20 patients (85% M1c) received CP as first-line treatment, 41 patients (90.2% M1c) had received at least one prior systemic therapy for metastatic disease. Main toxicities were myelosuppression, fatigue and peripheral neuropathy. Partial responses were noted in 4.9% of patients, stable disease in 23% of patients. No complete response was observed. Median progression free survival was 10 weeks. Median overall survival was 31 weeks. Response, progression-free and overall survival were equivalent in first- and second-line patients. 60 patients of 61 died after a median follow up of 7 months. Median overall survival differed for patients with controlled disease (PR+SD) (49 weeks) compared to patients with progressive disease (18 weeks). CONCLUSIONS: Among patients with metastatic melanoma a subgroup achieved disease control under CP therapy which may be associated with a survival benefit. This potential advantage has to be weighed against considerable toxicity. Since response rates and survival were not improved in previously untreated patients compared to pretreated patients, CP should thus not be applied as first-line treatment

HER2 expression in cervical cancer as a potential therapeutic target

BACKGROUND: Trastuzumab, a humanized monoclonal antibody against the HER2 receptor is currently being used in breast and other tumor types. Early studies have shown that a variable proportion of cervical carcinoma tumors overexpress the HER2 receptor as evaluated by diverse techniques and antibodies. Currently it is known that a tumor response to trastuzumab strongly correlates with the level of HER2 expression evaluated by the Hercep Test, thus, it seems desirable to evaluate the status of expression of this receptor using the FDA-approved Hercep Test and grading system to gain insight in the feasibility of using trastuzumab in cervical cancer patients. METHODS: We analyzed a series of cervical cancer cell lines, the primary tumors of 35 cases of cervical cancer patients and four recurrent cases, with the Hercep Test in order to establish whether this tumor type overexpress HER2 at level of 2+/3+ as trastuzumab is currently approved for breast cancer having such level of expression. RESULTS: The results indicate that only 1 out of 35 primary tumors cases overexpress the receptor at this level, however, two out of four recurrent tumors that tested negative at diagnosis shifted to Hercep Test 2+ and 3+ respectively. CONCLUSIONS: The low frequency of expression in primary cases suggests that trastuzumab could have a limited value for the primary management of cervical cancer patients, however, the finding of "conversion" to Hercep Test 2+ and 3+ of recurrent tumors indicates the need to further evaluate the expression of HER2 in the metastatic and recurrent cases

Considering Usual Medical Care in Clinical Trial Design

Liza Dawson and colleagues discuss the scientific and ethical issues associated with choosing clinical trial designs when there is no consensus on what constitutes usual care

Spatial patterns of mercury in biota of Adirondack, New York lakes

We studied the spatial distribution patterns of mercury (Hg) in lake water, littoral sediments, zooplankton, crayfish, fish, and common loons in 44 lakes of the Adirondacks of New York State, USA, a region that has been characterized as a “biological Hg hotspot”. Our study confirmed this pattern, finding that a substantial fraction of the lakes studied had fish and loon samples exceeding established criteria for human and wildlife health. Factors accounting for the spatial variability of Hg in lake water and biota were lake chemistry (pH, acid neutralizing capacity (ANC), percent carbon in sediments), biology (taxa presence, trophic status) and landscape characteristics (land cover class, lake elevation). Hg concentrations in zooplankton, fish and common loons were negatively associated with the lake water acid-base status (pH, ANC). Bioaccumulation factors (BAF) for methyl Hg (MeHg) increased from crayfish (mean log10 BAF = 5.7), to zooplankton (5.9), to prey fish (6.2), to larger fish (6.3), to common loons (7.2). MeHg BAF values in zooplankton, crayfish, and fish (yellow perch equivalent) all increased with increasing lake elevation. Our findings support the hypothesis that bioaccumulation of MeHg at the base of the food chain is an important controller of Hg concentrations in taxa at higher trophic levels. The characteristics of Adirondack lake-watersheds (sensitivity to acidic deposition; significant forest and wetland land cover; and low nutrient inputs) contribute to elevated Hg concentrations in aquatic biota

Clinical research in ovarian cancer: consensus recommendations from the Gynecologic Cancer InterGroup

The Gynecologic Cancer InterGroup (GCIG) sixth Ovarian Cancer Conference on Clinical Research was held virtually in October, 2021, following published consensus guidelines. The goal of the consensus meeting was to achieve harmonisation on the design elements of upcoming trials in ovarian cancer, to select important questions for future study, and to identify unmet needs. All 33 GCIG member groups participated in the development, refinement, and adoption of 20 statements within four topic groups on clinical research in ovarian cancer including first line treatment, recurrent disease, disease subgroups, and future trials. Unanimous consensus was obtained for 14 of 20 statements, with greater than 90% concordance in the remaining six statements. The high acceptance rate following active deliberation among the GCIG groups confirmed that a consensus process could be applied in a virtual setting. Together with detailed categorisation of unmet needs, these consensus statements will promote the harmonisation of international clinical research in ovarian cancer

Immunotherapy with MVA-BN®-HER2 induces HER-2-specific Th1 immunity and alters the intratumoral balance of effector and regulatory T cells

MVA-BN®-HER2 is a new candidate immunotherapy designed for the treatment of HER-2-positive breast cancer. Here, we demonstrate that a single treatment with MVA-BN®-HER2 exerts potent anti-tumor efficacy in a murine model of experimental pulmonary metastasis. This anti-tumor efficacy occurred despite a strong tumor-mediated immunosuppressive environment characterized by a high frequency of regulatory T cells (Treg) in the lungs of tumor-bearing mice. Immunogenicity studies showed that treatment with MVA-BN®-HER2 induced strongly Th1-dominated HER-2-specific antibody and T-cell responses. MVA-BN®-HER2-induced anti-tumor activity was characterized by an increased infiltration of lungs with highly activated, HER-2-specific, CD8+CD11c+ T cells accompanied by a decrease in the frequency of Treg cells in the lung, resulting in a significantly increased ratio of effector T cells to Treg cells. In contrast, administration of HER2 protein formulated in Complete Freund’s Adjuvant (CFA) induced a strongly Th2-biased immune response to HER-2. However, this did not lead to significant infiltration of the tumor-bearing lungs by CD8+ T cells or the decrease in the frequency of Treg cells nor did it result in anti-tumor efficacy. In vivo depletion of CD8+ cells confirmed that CD8 T cells were required for the anti-tumor activity of MVA-BN®-HER2. Furthermore, depletion of CD4+ or CD25+ cells demonstrated that tumor-induced Treg cells promoted tumor growth and that CD4 effector cells also contribute to MVA-BN®-HER2-mediated anti-tumor efficacy. Taken together, our data demonstrate that treatment with MVA-BN®-HER2 controls tumor growth through mechanisms including the induction of Th1-biased HER-2-specific immune responses and the control of tumor-mediated immunosuppression

What is known about the patient's experience of medical tourism? A scoping review

<p>Abstract</p> <p>Background</p> <p>Medical tourism is understood as travel abroad with the intention of obtaining non-emergency medical services. This practice is the subject of increasing interest, but little is known about its scope.</p> <p>Methods</p> <p>A comprehensive scoping review of published academic articles, media sources, and grey literature reports was performed to answer the question: what is known about the patient's experience of medical tourism? The review was accomplished in three steps: (1) identifying the question and relevant literature; (2) selecting the literature; (3) charting, collating, and summarizing the information. Overall themes were identified from this process.</p> <p>Results</p> <p>291 sources were identified for review from the databases searched, the majority of which were media pieces (<it>n </it>= 176). A further 57 sources were included for review after hand searching reference lists. Of the 348 sources that were gathered, 216 were ultimately included in this scoping review. Only a small minority of sources reported on empirical studies that involved the collection of primary data (<it>n </it>= 5). The four themes identified via the review were: (1) decision-making (e.g., push and pull factors that operate to shape patients' decisions); (2) motivations (e.g., procedure-, cost-, and travel-based factors motivating patients to seek care abroad); (3) risks (e.g., health and travel risks); and (4) first-hand accounts (e.g., patients' experiential accounts of having gone abroad for medical care). These themes represent the most discussed issues about the patient's experience of medical tourism in the English-language academic, media, and grey literatures.</p> <p>Conclusions</p> <p>This review demonstrates the need for additional research on numerous issues, including: (1) understanding how multiple information sources are consulted and evaluated by patients before deciding upon medical tourism; (2) examining how patients understand the risks of care abroad; (3) gathering patients' prospective and retrospective accounts; and (4) the push and pull factors, as well as the motives of patients to participate in medical tourism. The findings from this scoping review and the knowledge gaps it uncovered also demonstrate that there is great potential for new contributions to our understanding of the patient's experience of medical tourism.</p

Ovarian cancer immunotherapy: opportunities, progresses and challenges

Due to the low survival rates from invasive ovarian cancer, new effective treatment modalities are urgently needed. Compelling evidence indicates that the immune response against ovarian cancer may play an important role in controlling this disease. We herein summarize multiple immune-based strategies that have been proposed and tested for potential therapeutic benefit against advanced stage ovarian cancer. We will examine the evidence for the premise that an effective therapeutic vaccine against ovarian cancer is useful not only for inducing remission of the disease but also for preventing disease relapse. We will also highlight the questions and challenges in the development of ovarian cancer vaccines, and critically discuss the limitations of some of the existing immunotherapeutic strategies. Finally, we will summarize our own experience on the use of patient-specific tumor-derived heat shock protein-peptide complex for the treatment of advanced ovarian cancer

Ovarian cancer

Ovarian cancer is not a single disease and can be subdivided into at least five different histological subtypes that have different identifiable risk factors, cells of origin, molecular compositions, clinical features and treatments. Ovarian cancer is a global problem, is typically diagnosed at a late stage and has no effective screening strategy. Standard treatments for newly diagnosed cancer consist of cytoreductive surgery and platinum-based chemotherapy. In recurrent cancer, chemotherapy, anti-angiogenic agents and poly(ADP-ribose) polymerase inhibitors are used, and immunological therapies are currently being tested. High-grade serous carcinoma (HGSC) is the most commonly diagnosed form of ovarian cancer and at diagnosis is typically very responsive to platinum-based chemotherapy. However, in addition to the other histologies, HGSCs frequently relapse and become increasingly resistant to chemotherapy. Consequently, understanding the mechanisms underlying platinum resistance and finding ways to overcome them are active areas of study in ovarian cancer. Substantial progress has been made in identifying genes that are associated with a high risk of ovarian cancer (such as BRCA1 and BRCA2), as well as a precursor lesion of HGSC called serous tubal intraepithelial carcinoma, which holds promise for identifying individuals at high risk of developing the disease and for developing prevention strategies

Cell–cell and cell–matrix dynamics in intraperitoneal cancer metastasis

The peritoneal metastatic route of cancer dissemination is shared by cancers of the ovary and gastrointestinal tract. Once initiated, peritoneal metastasis typically proceeds rapidly in a feed-forward manner. Several factors contribute to this efficient progression. In peritoneal metastasis, cancer cells exfoliate into the peritoneal fluid and spread locally, transported by peritoneal fluid. Inflammatory cytokines released by tumor and immune cells compromise the protective, anti-adhesive mesothelial cell layer that lines the peritoneal cavity, exposing the underlying extracellular matrix to which cancer cells readily attach. The peritoneum is further rendered receptive to metastatic implantation and growth by myofibroblastic cell behaviors also stimulated by inflammatory cytokines. Individual cancer cells suspended in peritoneal fluid can aggregate to form multicellular spheroids. This cellular arrangement imparts resistance to anoikis, apoptosis, and chemotherapeutics. Emerging evidence indicates that compact spheroid formation is preferentially accomplished by cancer cells with high invasive capacity and contractile behaviors. This review focuses on the pathological alterations to the peritoneum and the properties of cancer cells that in combination drive peritoneal metastasis