Ketogenic metabolic therapy in conjunction with standard treatment for glioblastoma: A case report.

Glioblastoma (GBM) is the most common primary malignant brain tumour in adults. The standard of care consists of surgical resection and concurrent chemoradiation, followed by adjuvant temozolomide chemotherapy. This protocol is associated with a median survival of 12-15 months, and <5% of patients survive >3 years. Ketogenic metabolic therapy (KMT) targets cancer cell metabolism by restricting glucose availability and evoking differential stress resistance and sensitization, which may augment the standard treatments and lead to therapeutic benefit. The present study reports the case of a 64-year-old woman with isocitrate dehydrogenase (IDH)-wildtype GBM who pursued the standard treatment protocol in conjunction with an intensive, multimodal KMT program for 3 years. The KMT program consisted of a series of prolonged (7-day, fluid-only) fasts, which were specifically timed to maximize the tolerability and efficacy of the standard treatments, combined with a time-restricted ketogenic diet on all other days. During the first and second treatment years the patient sustained a glucose ketone index (GKI) of 1.65 and 2.02, respectively, which coincided with complete clinical improvement, a healthy body-mass index and a high quality of life, with no visible progressive tumour detected on imaging at the end of the second year. In the setting of the death of an immediate family member leading to increased life stress, slightly relaxed KMT adherence, and a higher GKI of 3.20, slow cancer progression occurred during the third year. The adverse effects attributed to KMT were mild. Despite the limitations of this case report, it highlights the feasibility of implementing the standard treatment protocol for GBM in conjunction with an intensive, long-term, multimodal and specifically timed KMT program, the potential therapeutic efficacy of which may depend upon achieving as low a GKI as possible.

Increased Expression of the Δ133p53ß Isoform Enhances Brain Metastasis.

The Δ133p53ß isoform is increased in many primary tumors and has many tumor-promoting properties that contribute to increased proliferation, migration and inflammation. Here we investigated whether Δ133p53ß contributed to some of the most aggressive tumors that had metastasized to the brain. Δ133p53ß mRNA expression was measured in lung, breast, melanoma, colorectal metastases and, where available, the matched primary tumor. The presence of Δ133p53ß expression was associated with the time for the primary tumor to metastasize and overall survival once the tumor was detected in the brain. Δ133p53ß was present in over 50% of lung, breast, melanoma and colorectal metastases to the brain. It was also increased in the brain metastases compared with the matched primary tumor. Brain metastases with Δ133p53ß expressed were associated with a reduced time for the primary tumor to metastasize to the brain compared with tumors with no Δ133p53ß expression. In-vitro-based analyses in Δ133p53ß-expressing cells showed increased cancer-promoting proteins on the cell surface and increased downstream p-AKT and p-MAPK signaling. Δ133p53ß-expressing cells also invaded more readily across a mock blood-brain barrier. Together these data suggested that Δ133p53ß contributes to brain metastases by making cells more likely to invade the brain.

Stereotactic ablative radiotherapy for early stage lung cancer and lung metastases in a New Zealand population.

AIM: Stereotactic ablative radiotherapy (SABR) involves the delivery of high doses of precisely targeted radiation in a shorter time period than conventional radiotherapy. The aim of this study was to compare the outcomes of lung-based SABR in a New Zealand cohort to the global literature. METHODS: A single-institution retrospective analysis was performed on all patients who received lung-based SABR between May 2015 and September 2019 at Waikato Hospital, New Zealand. The study included both early stage lung cancer and lung oligometastases that measured less than 5cm. RESULTS: 102 patients received SABR to 116 lesions. Median follow-up was 19 months. The three-year rate of local control in the primary and metastatic cohorts was 85% and 82%, respectively. This reflects the three-year local control rate of 86% for primary lung cancer in the SPACE trial and the two-year local control rate of 81% for pulmonary oligometastases in a German study. Central primary lung cancer was associated with a higher risk of local recurrence (HR6.4 (1.3-31.5) p=0.02). The three-year progression-free survival rate in patients with early stage lung cancer and oligometastases was 56% and 26%, respectively. Maori patients with primary lung cancer had a significantly worse progression free survival (HR2.4 (1.1-5.1) p=0.03). There were no reported grade three toxicities. CONCLUSION: The use of lung-based SABR in a typical radiotherapy setting in New Zealand mirrors global outcomes.

Extensive Pulmonary Metastases 13 Years after Initial Resection of Intracranial Meningioma.

BACKGROUND: Extracranial metastasis from intracranial meningioma is a very rare condition. A current literature review reveals that only few cases are documented with extensive pulmonary involvement >10 years after initial intracranial meningioma resection. Diagnosis of pulmonary meningioma is often confirmed by computed tomography chest-guided core biopsies. The prognosis of extensive metastatic pulmonary meningioma, however, is unknown and there is no gold standard treatment option. CASE DESCRIPTION: We present a case of multiple pulmonary meningioma metastases developing 13 years after initial resection of left occipital parafalcine World Health Organization Grade I intracranial meningioma. CONCLUSION: There are no established guidelines for the optimal management or surveillance of extensive pulmonary metastatic meningioma. In patients with high-grade meningioma and multiple cannonball pulmonary lesions, metastatic meningioma should be considered as part of the differential diagnosis. Metastatic meningioma may occur even a decade after initial tumour resection.

Outcomes after primary intensity-modulated radiation therapy for oropharyngeal squamous cell carcinoma at a New Zealand regional cancer centre: Impact of p16 status.

INTRODUCTION: The rising incidence of oropharyngeal squamous cell carcinoma (OPSCC) in New Zealand is due to an increase in the numbers of human papilloma virus (HPV)-associated OPSCC. We evaluated the impact of positive p16 immunohistochemistry, as a surrogate for HPV positivity, on OPSCC outcomes after primary intensity-modulated radiotherapy (IMRT) with or without concurrent chemotherapy. METHODS: Retrospective review was undertaken of electronic medical records of 90 patients with OPSCC who received primary IMRT with or without chemotherapy between 2008 and mid-2015 at the Regional Cancer Centre, Waikato Hospital, Hamilton, New Zealand. RESULTS: Median age was 57.5 years. Immunohistochemistry for p16 was positive in 53 (59%) OPSCC while 37 (41%) had negative or unknown p16 status. Median radiotherapy dose was 70 Gy. Chemotherapy was administered to 78 (87%) patients, most receiving high-dose cisplatin. Nine patients had residual disease following treatment completion. Seven patients relapsed, and 26 died during the study period. Five patients with p16-positive OPSCC had persistent or recurrent disease. Actuarial 3-year locoregional control, disease-free survival, and overall survival for all patients were 80.7%, 74.7%, and 77.1%, respectively. Among p16-positive OPSCC patients, 3-year locoregional control, disease-free survival, and overall survival were 89.5%, 80.8%, and 90.9%, respectively. CONCLUSION: Outcomes after IMRT for OPSCC at Waikato Hospital are in line with the reported literature. Human papilloma virus-related OPSCC has better outcomes compared with patients with unknown or HPV-unrelated OPSCC. Trials are underway evaluating reduced intensity of treatment for HPV-related OPSCC.

Early experience with novel immunomodulators for cancer treatment.

Immunotherapy involves the treatment of cancer by modification of the host-tumour relationship. It is now known that this relationship is quite complex and only some of the interactions have been elucidated. Early attempts at immunotherapy, such as Coley's toxins, were undertaken without an understanding of the processes mediating the effects. With a better understanding of the immunology of this anticancer response, recent trials have focussed on certain aspects of the process to stimulate an antitumour response. In this review, the authors discuss a number of novel biological response modifiers that work as general stimulants of the immune system, through varied mechanisms including induction of stimulatory cytokines (such as IFN-alpha, TNF-alpha and IL-12) and activation of T cells and the antigen-presenting dendritic cells. These compounds include Toll-like receptor agonists, several of which are in clinical trials at present. In addition to immunomodulatory activity, some compounds such as 5,6-dimethylxanthenone-4-acetic acid (DMXAA) and thalidomide and its analogues also target existing or developing tumour vasculature. Some of these compounds have single-agent activity in clinical trials, while others such as DMXAA have shown promise in combination with chemotherapy without increasing toxicity. Lactoferrin is another compound that has shown clinical activity with low toxicity. At present, accepted indications for immunotherapy are limited to a few cancers such as renal cell carcinoma and melanoma. This paper looks at some of the reasons for the limited impact of immunotherapy so far and suggest possible avenues for further research with a greater likelihood of success.

Chemotherapy prescription patterns in colon cancer: a patterns-of-care survey in New Zealand.

Colorectal cancer is the second most common site of cancer for both men and women in New Zealand (NZ). Survival, especially with metastatic disease, has improved considerably over the last decade with the introduction of new chemotherapeutic agents. A questionnaire-based survey was conducted to document variations in chemotherapy prescription patterns throughout NZ. Out of 25 medical oncologists, responses were obtained from 22 (88%). The patient with stage III colon cancer was offered either 5-fluorouracil/leucovorin, most commonly on the weekly bolus schedule, or capecitabine monotherapy. Chemotherapy was also offered by the majority (65%) of respondents to the patient with 'high-risk' stage II colon cancer. Several chemotherapy combinations are available in NZ in the metastatic setting, with the most popular being oxaliplatin/capecitabine combination (CAPOX) (35%) or irinotecan/5-FU combination (FOLFIRI) (23%). None of the respondents would commence chemotherapy solely on the basis of a rising carcinoembryonic antigen (CEA). Two-thirds of respondents would recommend chemotherapy for the patient with resectable liver metastases, either before or after surgery. Our survey indicates that chemotherapy prescriptions for patients with colon cancer in NZ, though not uniform, are mostly in line with international recommendations.

Baseline staging of newly diagnosed breast cancer--Kuwait cancer control center experience.

OBJECTIVE: To determine the value of staging investigations in detecting metastases in newly diagnosed asymptomatic patients with breast cancer. MATERIALS AND METHODS: A retrospective review of patients' files with newly diagnosed breast cancer in the period from 1993 to 1998 was performed. Due to inadequate information, thirty-eight files were excluded leaving 785 files for analysis. RESULTS: Of the total 785 patients, we found distant metastases at the time of primary diagnosis in 36 (4.6%) patients, bone metastases in 29 (3.7%) patients, pulmonary metastases in 6 (0.8%) patients and liver metastases in 5 (0.6%) patients. Overall, 0.7% of patients with clinical stage I and II disease had metastases compared with 16.2% of patients with clinical stage III disease (statistically significant p = 0.0001). CONCLUSION: The results confirm the low yield of routine bone scans, liver ultrasound and chest X-ray among patients with asymptomatic early-stage breast cancer. These tests are therefore not recommended for such patients, although intensive investigations are appropriate for more advanced tumors.