First Clinical Report of Proton Beam Therapy for Postoperative Radiotherapy for Non–Small-Cell Lung Cancer

Background and Purpose

The characteristic Bragg peak of proton beam therapy (PBT) allows for sparing normal tissues beyond the tumor volume that may allow for decreased toxicities associated with postoperative radiation therapy (PORT). Here we report the first institutional experience with proton therapy for PORT in patients with non–small-cell lung cancer (NSCLC) and assess early toxicities and outcomes.

Incidence of Second Malignancy after Successful Treatment of Limited-Stage Small–Cell Lung Cancer and Its Effects on Survival

IntroductionExtended survival outcomes from improved treatments for patients with cancer come with an increased risk for development of a metachronous second malignancy (MSM). We evaluated the incidence of MSM after successful treatment of SCLC and compared survival between patients with SCLC in whom MSM developed and those in whom it did not.MethodsSelection criteria were a diagnosis of limited-stage SCLC and receipt of at least 45 Gy of radiotherapy and chemotherapy at a single institution in 1985–2012. MSM was defined as a tumor of a different histologic type than the primary that appeared more than 2 years after the diagnosis of SCLC.ResultsOf 704 patients identified, 32 were excluded for lack of follow-up, 48 for having SCLC as MSM after treatment of another type of cancer, 37 for nonmelanoma skin cancer as MSM, and 46 for MSM within 2 years after SCLC diagnosis. Of the remaining 541 patients, 346 had recurrent SCLC, 180 had no second malignancy and no recurrence, and 15 (2.8%) had MSM (13 in a lung [eight adenocarcinomas and five squamous cell carcinomas], one sarcoma, and one acute myeloid leukemia). All 15 patients with MSM achieved complete response to the SCLC treatment. Overall survival was longer for patients with MSM than for patients with no other malignancies and no recurrence, with 10-year rates of 61.9% (95% confidence interval: 30.0%–82.6%) and 29.9% (95% confidence interval: 21.5%–38.6%), respectively (p = 0.03).ConclusionsLong-term survivors after treatment for SCLC should be made aware of the risk for MSM and the necessity of follow-up.     

Clinical Review of Iressa for the Treatment of NSCLC

Following development of basic science and the advancement of tumor molecular biology, molecular-target therapy has evolved as a new field for cancer treatment. The agents used act at specific target points such as receptors, kinases and signal transduction systems which are related to tumor growth. These actions result in inhibting proliferation, metastasis, vascularization, and promoting tumor apoptosis. Iressa （gefitinib） which is used for the treatment of NSCLC is a small molecular weight agent acting by inhibition of epidermal growth factor receptor-tyrosine kinase. Iressa was the first approved agent for target therapy for the treatment of NSCLC. This article focuses on the results from clinical trials and the potential of Iressa for the treatment of NSCLC.     

nab-Paclitaxel for the Treatment of Advanced Squamous Non–Small-Cell Lung Cancer: A Comprehensive Update

Despite advances in the treatment of patients with nonsquamous non–small-cell lung cancer (NSCLC), lung cancer remains a leading cause of death globally. Studies have demonstrated that survival varies according to histological subtype, and, in many cases, patients with squamous NSCLC have a poorer survival rate than those with nonsquamous NSCLC. For patients with squamous NSCLC, platinum-based doublets remain the standard first-line therapy option. This is in part because of the efficacy and safety concerns with some of the approved therapies and is secondary to the observation that many of the mutations targetable with currently approved therapies are rare in patients with squamous NSCLC. Recently, a subset analysis of a completed phase III trial demonstrated that use of nab-paclitaxel with carboplatin led to improved responses in patients with squamous NSCLC compared with solvent-based paclitaxel with carboplatin. In this review, the current experience and evolving role of nab-paclitaxel with carboplatin in the treatment of squamous NSCLC is discussed.     

An overview of the ACE project—Advocating for Clinical Excellence: Transdisciplinary palliative care education

Background. Excellence in palliative care demands attention to the multidimensional aspects of patient and family suffering, yet too few psycho-oncology professionals report adequate preparation in this vital area. Methods. A total of 148 competitively selected psychologists, social workers, and spiritual care professionals participated in intensive educational courses to enhance their palliative care delivery, leadership, and advocacy skills. Extensive process and outcome evaluations measured the effectiveness of this educational program. Results. To date, 2 national courses have been completed. The courses received strong overall evaluations, with participants rating increased confidence in defined palliative care skills. Conclusions. The initial results of this innovative National Cancer Institute-funded transdisciplinary training for psycho-oncology professionals affirm the need and feasibility of the program. See the Advocating for Clinical Excellence Project Web site (www.cityofhope.org/ACEproject) for additional course information.     

Clinical Characteristics and Prognosis of Patients With Advanced Non–Small-cell Lung Cancer Who Are Ineligible for Clinical Trials

Background

Most patients with non–small-cell lung cancer (NSCLC) are ineligible for clinical trials. However, few studies have reported on the profiles and treatment outcomes for these patients. Therefore, we investigated the characteristics, outcomes, and survival of patients with advanced NSCLC who were ineligible for clinical trials.

Solicit for Subscriptions of The Chinese-German Journal of Clinical Oncology

The Chinese-German Journal of Clinical Oncology, a medical academic periodical superintended by Chinese Educational Ministry, sponsored by Huazhong University of Science and Technology and cooperatively published by China-Germany , is issued and published as a united journal of Chinese-German Medical Association in China and German-Chinese Medical Association in Germany.     

Solicit for Subscriptions of The Chinese-German Journal of Clinical Oncology

The Chinese-German Journal of Clinical Oncology, a medical academic periodical superintended by Chinese Educational Ministry, sponsored by Huazhong University of Science and Technology and cooperatively published by China-Germany , is issued and published as a united journal of Chinese-German Medical Association in China and German-Chinese Medical Association in Germany.This jounral can be ordered at local post offices of China and also directly subscribed from Editorial Office of The Chinese-German Journal of Clinical Oncology.Publication on the 25th of the end of each quarter, Code No. BM 38-121Quarterly issued both internal and external     

Clinical Experience of Lobectomy With Pulmonary Artery Reconstruction for Central Non–Small-Cell Lung Cancer

BackgroundIn patients with central lung cancer, lobectomy can be achieved without pneumonectomy by surgical reconstruction of the pulmonary artery (PA). Herein, we report our clinical experience of 34 patients who had lobectomy with PA reconstruction, including perioperative administration, morbidity, mortality, and long-term survival.Patients and MethodsThe clinical records of 34 patients who received lobectomy with PA reconstruction in our department between August 2003 and September 2005 were reviewed.ResultsIn our series, PA reconstruction with end-to-end anastomosis was performed in 18 patients (52.9%). Seven patients (20.6%) required partial PA reconstruction with autologous pericardium patch. Five patients (14.7%) with a lower lobe tumor required PA reconstruction with artery flap. The perioperative mortality was 2.9%, and 1 patient died on postoperative day 13 because of severe bronchopleural fistula. Another 2 patients had acute respiratory distress syndrome (ARDS) and required reintubation in our Intensive Care Unit. The overall Kaplan-Meier 3-year and 5-year survival rates were 46% and 37%, respectively. As compared with the stage III patients, stage I patients had significantly greater 5-year survival (80% vs. 11%; P = .005). Patients with pN0 disease also had greater 5-year survival than patients with pN2-3 disease (71% vs. 9%; P = .004).ConclusionIn our department, PA reconstruction has been more frequently and actively performed for patients with central lung cancer, especially for some patients with a lower lobe tumor. Although the morbidity and mortality is acceptable, surgeons should be more attentive to lethal postoperative complications such as ARDS induced by lung ischemia-reperfusion injury.     

Efficacy of Immediate Postoperative Instillation of Chemotherapy for Primary Non–Muscle-Invasive Bladder Cancer in Real-World Clinical Practice

BackgroundNon–muscle-invasive bladder cancer (NMIBC) can be treated using transurethral resection (TUR), but high incidence of intravesical recurrence remains a clinical challenge. Single immediate postoperative instillation of chemotherapy (IPIOC) is controversial for NMIBC patients with intermediate recurrence risk. The aim of the present study was to report the efficacy and toxicity of IPIOC, particularly in intermediate-risk NMIBC patients, in the real-world setting.Patients and MethodsWe retrospectively analyzed 363 consecutive patients with primary NMIBC who underwent radical TUR at Kyoto University Hospital between 2007 and 2016.ResultsIn low-risk patients, recurrence-free survival (RFS) was significantly better for IPIOC than non-IPIOC (2-year RFS: 89.3% vs. 59.4%; P = .001). In intermediate-risk patients, IPIOC was associated with significantly longer RFS compared with non-IPIOC (2-year RFS: 85.5% vs. 58.2%; P = .011). IPIOC and bacillus Calmette-Guérin (BCG) were independent predictors for post-TUR recurrence (non-IPIOC vs. IPIOC: hazard ratio [HR], 2.33; 95% confidence interval [CI], 1.14-4.88; P = .02; non-BCG vs. BCG: HR, 2.22; P = .045, 95% CI, 1.02-5.30). In the high-risk group, only BCG was an independent prognostic factor of recurrence in a multivariate Cox proportional hazards model (HR, 2.55; P = .006, 95% CI, 1.32-4.87). There were no significant differences between the BCG-only group and the IPIOC with BCG group in Grade 3 or more local (16 patients [21%] vs. 21 patients [24%]; P = .61) or systemic (3 patients [4%] vs. 6 patients [7%]; P = .40) toxicity rates.ConclusionOur study showed the efficacy of IPIOC for the prevention of intravesical recurrence in primary intermediate-risk NMIBC patients regardless of BCG therapy.     

Expression of Survivin Gene and Its Relationship with Clinical Multidrug Resistance in Osteosarcoma

Objective: To study the expression of survivin and its relationship with clinical multidrug resistance in osteosarcoma. Methods: By using immunohistochemistry (S-P) method, the expression of Survivin in osteosarcoma, osteochondroma and normal osseous tissue, and the expression of P-glycoprotein in osteosarcoma was detected. Results: Survivin positive expression rate was 65.71% in osteosarcoma, but no expression of Survivin was detectable in osteochondroma and normal osseous tissue. The positive expression rate of Survivin was significantly associated with Enneking clinical stages and histological typing (WHO), but no relationship was found among Survivin expression and age, sex and tumor location. The positive expression rate of P-glycoprotein was 45.71%. There was a significant correlation between Survivin and p-glycoprotein. Conclusion: Survivin overexpression was significantly associated with clinical multidrug resistance in osteosarcoma. It could be a potential target for treatment of osteosarcoma.     

The Lack of Antitumor Effects of o,p′DDA Excludes Its Role as an Active Metabolite of Mitotane for Adrenocortical Carcinoma Treatment

Mitotane (o,p′DDD) is the most effective treatment of advanced adrenocortical carcinoma (ACC) but its mechanism of action remains unknown. Previous studies suggested that o,p′DDA may represent the active metabolite of mitotane. We aimed at reevaluating the potential role and pharmacological effects of o,p′DDA. Functional consequences of o,p′DDA exposure were studied on proliferation, steroidogenesis, and mitochondrial respiratory chain in human H295R and SW13 adrenocortical cells. Mitotane and its metabolites were quantified using high-performance liquid chromatography combined to an ultraviolet detection in these cells treated with o,p′DDD or o,p′DDA and in human adrenal tissues. Dose–response curves up to 300 μM showed that, as opposed to o,p′DDD, o,p′DDA did not inhibit cell proliferation nor alter respiratory chain complex IV activity, gene expression nor induce mitochondrial biogenesis, oxidative stress, or apoptosis. However, whereas mitotane drastically decreased expression of genes involved in steroidogenesis, o,p′DDA slightly reduced expression of some steroidogenic enzymes and exerts weak anti-secretory effects only at high doses. While o,p′DDD concentration was significantly reduced by 40 % in H295R cell supernatants after 48 h incubation, o,p′DDA levels remained unchanged suggesting that o,p′DDA was not efficiently transported into the cells. o,p′DDA was not detected in cell homogenates or supernatants after 48 h exposure to o,p′DDD, consistent with the absence of o,p′DDA production in these models. Finally, unlike o′p′DDD, we found that o,p′DDA content was undetectable in two ACC and one normal adrenal gland of mitotane-treated patients, suggesting a lack of cellular uptake and in situ production. Our results demonstrate that o,p′DDD, but not o,p′DDA, induces functional alterations in adrenal cells.     

Clinical and Economic Value of Genetic Sequencing for Personalized Therapy in Non–small-cell Lung Cancer

Two recent studies examining the clinical and economic value of next-generation sequencing (NGS)-based diagnostic testing (multi-gene panel examining ≥ 30 genes) for non–small-cell lung cancer therapy compared with single gene ALK, EGFR testing to select therapy demonstrated statistically insignificant improvement in population-level overall survival and only a moderate incremental cost-effectiveness ratio associated with the NGS testing approach. The data, however, revealed a key practice gap: many patients with actionable mutations did not receive targeted therapies. This gap is attributed, in part, to limitations in the availability and interpretation of NGS results, sample processing constraints, limited access to targeted therapies, and lagging awareness of the rapidly evolving field of personalized medicine, all of which result in “clinical inertia,” (ie, suboptimal use of targeted therapy against an actionable driver alteration identified by NGS testing). Additional analysis estimated that cost-effectiveness would improve significantly if a higher percentage of patients received testing and if all patients who were eligible for targeted therapies received them. Strategies to address implementation barriers will help to realize the full value of NGS testing in cancer care.