Triple-negative breast cancer (TNBC) is more aggressive and metastatic than other breast cancer types. Cytotoxic chemotherapy is presently the predominant systemic therapy for TNBC patients. This case report highlights the influence of metabolically supported chemotherapy (MSCT), ketogenic diet (KD), hyperthermia (HT), and hyperbaric oxygen therapy (HBOT) in an overweight 29-year-old woman with stage IV (T4N3M1) triple-negative invasive ductal carcinoma of the breast. The patient presented with an observable mass in her left breast detected during a physical examination in December 2015. Magnetic resonance imaging revealed a Breast Imaging Reporting and Data System Category 5 tumor and multiple lymphadenomegaly in the left axilla. A Tru-Cut biopsy led to the diagnosis of a triple-negative nuclear grade 2 invasive ductal carcinoma. The patient was admitted to ChemoThermia Oncology Center, Istanbul, Turkey in October 2016, and a whole body (18F)-fluorodeoxyglucose (FDG)-positron emission tomography-computed tomography (PET-CT) scan revealed a 77 mm x 55 mm primary tumor in her left breast, multiple left pectoral and axillary lymph nodes, multiple widespread liver masses, and an upper left nodular abdominal lesion. The patient received a treatment protocol consisting of MSCT, KD, HT, and HBOT. A follow-up whole body 18F-FDG PET-CT scan in February 2017 showed a complete therapeutic response with no evidence of abnormal FDG uptake. The patient continued to receive this treatment protocol and in April 2017 underwent a mastectomy, which revealed a complete pathological response consistent with the response indicated by her PET-CT imaging. This single case study presents evidence of a complete clinical, radiological, and pathological response following a six-month treatment period using a combination of MSCT and a novel metabolic therapy in a patient with stage IV TNBC.

Background: Previous evidence suggests that metabolically supported chemotherapy (MSCT), ketogenic diet, hyperthermia and hyperbaric oxygen therapy (HBOT) could all target vulnerabilities of cancer cells. This study aimed to evaluate the efficacy and the tolerability of this combination therapy in the treatment of stage IV non-small cell lung cancer (NSCLC). Methods: Forty-four NSCLC patients with distant metastasis that received MSCT (administration of chemotherapy regimen following induced hypoglycemia) plus ketogenic diet, hyperthermia and HBOT combination were included in this retrospective study. Survival and treatment response rates as well as toxicities were evaluated. Results: Overall response rate (ORR, complete response plus partial response) was 61.4%; whereas, 15.9% and 22.7% of patients had stable disease (SD) and progressive disease (PD), respectively. Mean overall survival (OS) and progression-free survival (PFS) was 42.9 months (95% CI: 34.0-51.8) and 41.0 months (95% CI: 31.1-50.9), respectively. A higher Eastern Cooperative Oncology Group (ECOG) performance status (ECOG !2) was associated with worse OS and PFS. Patients received chemotherapy cycles with acceptable toxicity and adverse events. No problems were encountered due to fasting, hypoglycemia, ketogenic diet, hyperthermia or hyperbaric oxygen therapy. Conclusions: Findings of this study suggest that MSCT combined with other modalities targeting multiple pathways and cellular vulnerabilities may bring about remarkable improvements in survival outcomes and treatment response rates in metastatic NSCLC, without additional safety concerns. Large comparative studies are warranted to draw robust conclusions.

Background: Despite introduction of new chemotherapeutic agents, outcomes of patients with metastatic pancreatic cancer are still poor. Metabolically supported chemotherapy (MSCT) is a novel approach targeting dysregulated energy mechanism of the tumor cell. Objectives: This study aimed to examine the efficacy of metabolically supported administration of chemotherapy combined with ketogenic diet, hyperthermia, and hyperbaric oxygen therapy (HBOT) in patients with metastatic pancreatic cancer. Method: This retrospective observational study included 25 patients with metastatic pancreatic ductal carcinoma (stage IV) who received MSCT (either gemcitabine-based or FOLFIRINOX regimen administered concomitantly with induced hypoglycemia) plus ketogenic diet, hyperthermia, and HBOT combination. Survival outcomes were evaluated. Results: During the mean follow-up duration of 25.4 ± 19.3 months, median overall survival and median progression-free survival were 15.8 months (95% CI, 10.5–21.1) and 12.9 months (95% CI, 11.2–14.6), respectively. Age and gender did not have any effect on overall survival (p > 0.05 for all). Conclusions: MSCT administered together with ketogenic diet, hyperthermia, and HBOT appears to be a viable option with the potential to improve survival outcomes in patients diagnosed with metastatic pancreatic cancer. Further research, particularly with larger comparative clinical trials, is warranted.

Breast cancer remains as a significant cause of morbidity and mortality in women. Ultrastructural and biochemical evidence from breast biopsy tissue and cancer cells shows mitochondrial abnormalities that are incompatible with energy production through oxidative phosphorylation (OxPhos). Consequently, breast cancer, like most cancers, will become more reliant on substrate level phosphorylation (fermentation) than on oxidative phosphorylation (OxPhos) for growth consistent with the mitochondrial metabolic theory of cancer. Glucose and glutamine are the prime fermentable fuels that underlie therapy resistance and drive breast cancer growth through substrate level phosphorylation (SLP) in both the cytoplasm (Warburg effect) and the mitochondria (Q-effect), respectively. Emerging evidence indicates that ketogenic metabolic therapy (KMT) can reduce glucose availability to tumor cells while simultaneously elevating ketone bodies, a non-fermentable metabolic fuel. It is suggested that KMT would be most effective when used together with glutamine targeting. Information is reviewed for suggesting how KMT could reduce systemic inflammation and target tumor cells without causing damage to normal cells. Implementation of KMT in the clinic could improve progression free and overall survival for patients with breast cancer.

Background: Angiogenesis is one of the key steps in solid tumor growth and metastasis. We planned to investigate the prognostic significance of vascular endothelial growth factor (VEGF), hypoxia-inducible factor 1α (HIF-1α) and CD34 expressions as markers of angiogenesis in gastric cancer. Patients and Methods: We retrospectively reviewed the medical records of 51 gastric cancer patients who had total or subtotal gastrectomy at Marmara University Hospital from 1990 to 2004 and evaluated the expression of VEGF, HIF-1α and CD34 by immunohistochemistry in their archival tumor tissues. We recorded the clinical and pathological characteristics of these patients and analyzed their survival outcome. Results: Thirty out of 51 patients were males. The median age was 63 years (range 34–81). The median follow-up was 17 months. Thirty-six patients had node-positive disease. The majority of patients (n = 43) had T2 and T3 disease. Vascular and lymphatic invasions were present in 57 and 77% of tumors, respectively. VEGF and HIF-1α were positive in 65 and 71% of tumors. The median CD34 staining score was 19 (3–68). VEGF, HIF-1α and CD34 expressions were more frequent in tumors without serosal invasion (p = 0.01, p = 0.01 and p = 0.003, respectively). CD34 expression was significantly more frequent in tumors with VEGF and HIF-1α expression (p = 0.00, p = 0.00). HIF-1α expression was more frequent in tumors with VEGF expression (p = 0.00). The 5-year overall survival was 45%. VEGF, HIF-1α, CD34 expressions and other pathological characteristics were found to have no impact on survival. Conclusion: VEGF, HIF-1α and CD34 expressions were more common in tumors without serosal invasion. As a future perspective, biological agents targeting VEGF and HIF-1α might be more effective at earlier stages of gastric cancer.

Aim: Systemic chemotherapy is a part of multi-modality treatment in patients with stage II-IV rectal cancer. In particular, patients not eligible for curative resection at the time of diagnosis require more efficient approaches to improve outcomes. Metabolically supported chemotherapy (MSCT) is a novel approach targeting dysregulated energy mechanism of the tumor cell. This study aimed to examine the efficacy of MSCT combined with ketogenic diet, hyperthermia and hyperbaric oxygen therapy (HBOT) in patients with stage II-IV rectal cancer not eligible for surgery at baseline. Methods: Twenty-one patients diagnosed with stage II-IV rectal carcinoma who received metabolically supported chemotherapy (MSCT) combined with ketogenic diet, hyperthermia and HBOT were included. Firstline chemotherapy regimen was oxaliplatin-based, whereas second line regimen was irinotecan-based. Overall survival and progression-free survival were estimated. Results: Mean duration of follow-up was 33.3±22.0 months. Mean overall survival was 58.6 months (95% CI, 43.3-73.9) and corresponding figure for progression-free survival was 45.1 months (95% CI, 28.9-61.2). Mean overall survival for patients with metastatic disease was 35.7 months. Multivariate analysis identified male gender and stage IV disease as independent predictors of worse progression free survival. No other parameter effected survival outcomes. Conclusion: Findings of this study are promising for potential use of this novel combinatorial protocol targeting multiple vulnerabilities of tumor cells in patients with advanced rectal cancer, particularly for patients with metastatic disease, without additional safety concerns. However, long term results are warranted to draw firm conclusion.

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