Michael Sanatani

Management and Prognosis in Synchronous Solitary Resected Brain Metastasis from Non–Small-Cell Lung Cancer

BACKGROUND Reports in the medical literature have described cases of extended survival of patients with non-small-cell lung cancer (NSCLC) with solitary metastatic disease who have received aggressive treatment both to the brain metastasis and to the local/regional disease. The objective of this research is to analyze prognostic factors that predict for outcome in this unique patient population. PATIENTS AND METHODS A single-institution, retrospective chart review was performed on 35 patients with NSCLC and a synchronous solitary brain metastasis (SSBM) treated with craniotomy and whole-brain radiation therapy. Eight patients (22.9%) had chest surgery, 24 (68.6%) had chemotherapy, and 14 (40%) had thoracic radiation as part of their local management. Fourteen had stage I/II disease (42.9%), and 20 had stage III disease (57.1%). Mean age at diagnosis was 58.5 years. Eighteen patients (56.25%) had a brain metastasis < 3 cm, and 14 patients (43.75%) had a metastasis > 3 cm. RESULTS Median survival was 7.8 months, and at last follow-up, 3 patients (8.6%) were alive and well, 6 patients (17.1%) were alive and with disease, 24 patients (68.6%) had died of disease, and 2 patients (5.7%) had died of other causes. Univariate analysis demonstrated that lung surgery (P = .0033), primary lung treatment > 8 weeks after brain surgery (P = .0128), and stage I/II disease (P = .0467) were predictive of overall survival. CONCLUSION Survival remains poor for patients with NSCLC with an SSBM. However, patients with thoracic disease amenable to local resection should be considered for such therapy because a survival advantage could exist compared with patients with more locally advanced disease.

Age and Comorbidity Considerations Related to Radiotherapy and Chemotherapy Administration

Oncological treatment decision-making is a highly complex enterprise integrating multiple patient, tumor, treatment, and professional factors with the available medical evidence. This management complexity can be exacerbated by the interplay of patient age and comorbid non-cancer conditions that can affect patient quality of life, treatment tolerance, and survival outcomes. Given the expected increase in median age (and associated comorbidity burden) of Western populations over the next few decades, the use of evidence-based therapies that appropriately balance treatment intensity and tolerability to achieve the desired goal of treatment (radical, adjuvant, salvage, or palliative) will be increasingly important to health care systems, providers, and patients. In this review, we highlight the evidence related to age and comorbidity, as it relates to radiotherapy and chemotherapy decision making. We will address evidence as it relates to age and comorbidity considerations separately and also the interplay between the factors. Clinical considerations to adapt radiation and/or chemotherapy treatment to deal with comorbidity challenges will be discussed. Knowledge gaps, future research, and clinical recommendation in this increasingly important field are highlighted as well.

Feasibility of an exercise intervention for fatigued breast cancer patients at a community-based cardiac rehabilitation program

Purpose Exercise is beneficial to quality of life after cancer treatment, yet few cancer survivors meet exercise guidelines. Our study sought to determine the feasibility of an oncology rehabilitation exercise program embedded within a cardiac rehabilitation program. Methods Patients who rated their fatigue >4/10 after completion of adjuvant chemotherapy for breast cancer were screened for eligibility and the outcomes were assessed (Piper Fatigue Scale, Functional Assessment of Cancer Therapy-Breast [FACT-B], Edmonton Symptom Assessment System, body composition, stress test, and physical activity measurement [accelerometer]). Participants received individualized exercise prescription. Following the 16-week program, repeat assessment plus patient acceptance and satisfaction survey was completed. The primary end point was the composite of accrual rate >25%, program adherence >80%, and mean compliance with accelerometer use >80%. Results Twenty of 24 screened patients consented to the study and completed the baseline assessment. Adherence was 30.3%. Mean accelerometer use was 3.88/7 days (78%). Fatigue at baseline was rated at 4.82/10, and at 3.59 (p = 0.09) after the intervention. Overall well-being (FACT-B) score changed from 92.7 to 98.3 (p = 0.05). There were no significant changes in body composition (except for bone mineral content), aerobic exercise capacity, or activity patterns. Conclusion Although the primary outcome was not met, our study indicates that an oncology exercise rehabilitation program can be incorporated into an existing cardiac rehabilitation program. Based on feedback received, we propose that in order to achieve exercise goals, frequent, encouraging, and tailored feedback and group sessions to foster a sense of community may additionally be needed to strengthen adherence to a prescribed exercise program.

Analysis of a Novel Protocol of Combined Induction Chemotherapy and Concurrent Chemoradiation in Unresected Non-Small- Cell Lung Cancer: A Ten-Year Experience With Vinblastine, Cisplatin, and Radiation Therapy

BACKGROUND The London Regional Cancer Program (LRCP) uses a unique schedule of induction plus concurrent chemoradiation, termed VCRT (vinblastine, cisplatin, and radiation therapy), for the treatment of a subset of unresectable stage IIIA and IIIB non-small-cell lung cancer (NSCLC). This analysis was conducted to better understand the outcomes in VCRT-treated patients. PATIENTS AND METHODS We report a retrospective analysis of a large cohort of patients who underwent VCRT at the LRCP over a 10-year period, from 1996 to 2006. The analysis focused on OS, toxicities, and the outcomes from completion surgery in a small subset of patients. RESULTS A total of 294 patients were included and 5-year OS, determined using Kaplan-Meier methodology, was 19.8% with a MST of 18.2 months. Reported grade 3-4 toxicities included neutropenia (39%), anemia (10%), pneumonitis (1%), and esophagitis (3%). Significant differences in survival between groups of patients were demonstrated with log-rank tests for completion surgery, use of radiation therapy, and cisplatin dose. Similarly, Univariate Cox regression showed that completion surgery, use of radiation therapy, cisplatin dose, and vinblastine dose were associated with increased survival. CONCLUSION This retrospective analysis of a large cohort of patients reveals an OS for VCRT comparable to that reported in the literature for other current combined chemoradiation protocols. The success of this protocol seems to be dose dependent and the outcomes in those who underwent completion surgery suggests that pathologic complete remission is possible for IIIA and IIIB NSCLC.

Phase II trial of capecitabine plus erlotinib versus capecitabine alone in patients with advanced colorectal cancer.

Aim & methods: Capecitabine monotherapy as palliation for advanced colorectal cancer (CRC) is generally well tolerated. Adding erlotinib, an EGFR-tyrosine kinase inhibitor, might improve efficacy versus capecitabine alone. 82 patients received capecitabine alone (Arm 1) or capecitabine with erlotinib (Arm 2). RESULTS Median time-to-progression (TTP) in Arm 1 was 7.9 months versus 9.2 in Arm 2. In KRAS-wild type (WT) patients TTP was 8.4 and 11.7 months in Arms 1 and 2, respectively. In KRAS-mutated patients TTP was 7.4 and 1.9 months in Arms 1 and 2, respectively (p = 0.023). Arm 2 KRAS-WT patients, left-sided primaries, had an overall survival of 16.0 versus 12.1 months in right-sided primaries. CONCLUSION Adding erlotinib to capecitabine increased TTP by 3.2 months in KRAS-WT patients. This study suggests that erlotinib harms patients with KRAS-mutated advanced CRC while it may provide benefit to those with KRAS-WT CRC. Further study of EGFR-tyrosine kinase inhibitors in patients with left-sided KRAS-WT CRC is warranted.

Balancing risk and benefit for first-line treatment of metastatic colorectal cancer: a graphic communication tool for patients and physicians.

Advances in the treatment of metastatic colorectal cancer have improved overall survival (OS); however, this might come at the cost of increased toxicity. Health-related quality of life, a significant concern closely related to toxicity and important when discussing palliative therapy, is infrequently assessed and reported in older clinical trials. As the number of tested regimens increases, the question arises on how to best present palliative treatment options. We present a simple way to compare treatment options in terms of potential risks and benefits. The literature was surveyed for reports of first-line systemic chemotherapies for metastatic colorectal cancer. The largest recent reports with detailed toxicity data were selected as representative for a regimen. Toxicity sum of a regimen was calculated as percent occurrences in the study cohort of severe adverse effects: diarrhea, mucositis, neurocutaneous conditions (excluding alopecia), vomiting, and febrile neutropenia. Limitations of toxicity reporting precluded inclusion of other or milder adverse events. Benefits (OS and progression-free survival [PFS]) were plotted graphically as benefit versus toxicity sum. Thirty-four regimens were found. Overall survival, PFS, and toxicity sum ranged from 8.9-24.7 months, 4.9-9.2 months, and 12-70 months, respectively. Weaknesses of our study include omission of some specific toxicities and of symptom control benefit, as well as heterogeneity of trial design and study populations. Furthermore, more recent OS data might reflect the availability of more lines of therapy rather than the effect of the first-line regimen, as comparison with PFS outcomes show. Our comparative tool helps physicians discuss the large number of available options with a patient in order to arrive at the treatment plan most appropriate to the individual and improve informed consent and disclosure, while highlighting limitations in available evidence.

Bilateral Blindness Following Chemoradiation for Locally Advanced Oropharyngeal Carcinoma.

Wernickes encephalopathy is a life-threatening neurologic complication of thiamine deficiency. Though the presentation of symptoms can vary widely, the classical triad is founded on ophthalmoplegia, alteration of mental status, and gait disturbance. We describe a case of Wernickes encephalopathy in an oncology patient shortly after concurrent 5-fluorouracil, carboplatin, and radiotherapy for locally advanced oropharyngeal cancer, presenting as complete bilateral blindness, ataxia, nystagmus, and confusion. Thiamine was given based on clinical suspicion and rapid improvement of clinical findings occurred. An MRI performed later supported the diagnosis of Wernickes encephalopathy. A multifactorial etiology of thiamine deficiency from nutritional deficits and neurotoxic effects of chemotherapy are hypothesized.

Follow-up Visits and Changes in Pain Scores Reported by Oncology Outpatients After Initial Presentation With Severe Pain

Background In addition to tumour treatment, the management of symptoms such as pain is an important component of cancer care. Pain management is a complex field and prior studies have highlighted many different clinical care responses to a cancer patient presenting with severe pain. We explored follow-up and how pain screening scores changed over time, among a cohort of cancer outpatients, and how follow-up was scheduled after the initial visit. Methods The care provided to 96 patients seen at the London Regional Cancer Program was reviewed for the 12-week period following presentation with severe pain >7/10. Follow-up ESAS (Edmonton Symptom Assessment System) scores, visits, and compliance were documented. Results Follow-up ESAS data was available for 41/96 patients. Mean ESAS pain decreased from 8.4/10 to 3.6/10 among those patients with follow-up; however, for 55/96 patients, no follow-up ESAS score was available (deceased n=3, no follow-up visit n=41, no pain score reported, n=11). Conclusions Despite a very high proportion of documented active pain management plans in the case of cancer patients presenting with severe pain, very little follow-up directed specifically at pain management was performed. Cancer treatment appears to be the primary determinant of oncology follow-up timing at our centre.

Use of alkylating chemotherapy in high-grade neuroendocrine tumours: Evaluation of real-world data.

78 Background: High-grade neuroendocrine tumours (NETs) are believed to have activity to certain alkylating agents, although data are scant. These regimens include streptozotocin (STZ) (used in combination with doxorubicin or 5-fluorouracil) and dacarbazine (DTIC). Current series report variable responses between 6 - 69%. Our objective was to evaluate our real world data to better understand treatment decision-making and clinical outcomes with alkylating agents in advanced high-grade NETs. METHODS We reviewed the medical records of 36 patients with metastatic NETs who received alkylating systemic chemotherapy with either a DTIC regimen (n = 15) or STZ based regimen (n = 21). Patient cases were evaluated for age, time to treatment failure (TTF), time to progression (TTP Results: Among 36 patients treated, the predominant primary NET was pancreas (n = 28) with a median age at treatment of 61.9 years. Observed TTF was similar with both regimens (STZ: 3 months and DTIC: 4 months), however there was prolonged TTP of 11 months with STZ vs. 5.3 months with DTIC (p = 0.047). There was no significant difference in OS with a mean of 48.7 months (DTIC) vs. 47.6 months (STZ) (p = 0.47). Baseline progression at treatment initiation was higher in DTIC at 77% versus 57% in STZ. The predominant cause of treatment discontinuation in both groups was progressive disease; DTIC (71%) versus STZ (42%). Toxicity resulted in treatment discontinuation in 19% for STZ vs 7% for DTIC. Other causes of treatment cessation were completion of the intended treatment. CONCLUSIONS In the groups evaluated, STZ containing regimens demonstrated prolonged PFS in comparison to DTIC, but there was no difference in OS between the two groups. Additionally, despite STZ appearing to have an increased toxicity rate, the rate of cessation between the groups was similar. This real world evaluation suggests similar efficacy with improved tolerability of DTIC based chemotherapy as a potential alternative to other alkylating agents.

Tolerability of the combination of ginger (Zingiber officinalis), gentian (Gentiana lutea) and turmeric (Curcuma longa) in patients with cancer-associated anorexia.

Abstract Background: Anorexia is a common symptom for patients with advanced cancer. Gentian, ginger, and turmeric have traditionally been used to stimulate appetite. We tested these agents in combination, in a pilot study to assess tolerability in patients indicating 4/10 or worse anorexia on the Edmonton Symptom Assessment System, and who were not currently on chemotherapy. We collected exploratory data on the patient’s appetite using a visual analogue scale. Methods: Between 2009 and 2012, 17 patients were enrolled in arm 1 (turmeric 1 g and ginger 1 g orally twice daily, and gentiana lutea tincture 1 mL three times a day, for 14 days). The three patients enrolled in arm 2 received the same doses of ginger and turmeric but no gentian. All patients completed a daily appetite diary and a weekly symptom assessment. Results: In arm 1, seven patients (41%) completed treatment. Seven patients (41%) stopped early because of unacceptable toxicity or patient-initiated discontinuation, and 3 stopped because of other reasons. All patients in arm 2 stopped taking the study medication within few days of starting the treatment, leading the study committee to recommend stopping the trial. The most common adverse effects attributed to study drugs were nausea (6 patients), vomiting (3), fatigue (3), diarrhea (2) and bloating (2). There was no statistically significant effect seen on appetite. Conclusions: At the doses used in this study, the combination of ginger, turmeric, and gentian is not tolerated well in cancer patients. Future studies should use fewer agents or lower doses.