Current Cancer Therapy Reviews

In the past few years, celebrities like Gord Downie in Canada and Robert Kennedy of the United States were diagnosed with glioblastoma. This heightened the interest in central nervous system (CNS) tumors among the general public. This thematic issue covers different aspects of management for CNS tumors. Although CNS tumors are only at around the 14th position among the common tumors in the world, but mortality is high [1]. The current role and recent advances of imaging, staging, pathology, surgery, radiotherapy and systemic therapies are reviewed. Recent changes to the World Health Organization (WHO) classification published in 2016 have demonstrated the prognostic and predictive value of molecular profiling and have also defined a new tumor entity diffuse midline glioma, histone H3-K27M mutant, as WHO grade IV [2]. In 2017, the eighth edition of American Joint Commission on Cancer staging has been introduced [3]. We have invited authors from different departments (dept.) and universities (U.) of Canada, France and Hong Kong so that readers would have a balanced view of treatment approaches and resources available in different countries. The review from Hong Kong by Prof. Dora Kwong’s group summarized the local experience and clinical trials to see if new treatments can be applied to the Oriental population. Modern technologies with image-guided radiotherapy (RT) or stereotactic RT improve the precision of radiation treatment and minimize toxicity. This editorial highlights a few controversies and updates mentioned below. Temozolomide (TMZ) emerged to be the cornerstone for glioblastoma treatment in 2005. In the landmark study of Stupp et al. 6 cycles of adjuvant TMZ were employed [4]. The duration of maintenance TMZ varies in different institutions, from 6-12 months [5]. Different dosages and timing of TMZ are described. Of interest, in the elderly patients with glioblastoma, the addition of TMZ to short-course radiotherapy resulted in longer survival than the short-course radiotherapy alone. TMZ (75/m2) was given concurrently with the radiation of total dose of 40 Gy, administered in 15 daily fractions over 3 weeks in patients 65 years older. Adjuvant TMZ was given for 12 cycles or until disease progression. The addition of TMZ to radiation resulted in improved survival compared with radiation alone (9.3 vs. 7.6 months), progression-free survival (PFS) was also improved (5.3 vs. 3.9 months). Among patients with O(6)-methylguanine DNA methyltransferase (MGMT) methylated tumors, the addition of TMZ improved overall survival (OS) by nearly six months (13.5 vs. 7.7 months), TMZ also appeared to improve survival in patients with MGMT unmethylated tumors (but the magnitude of effect was smaller: 10 vs. 7.9 months) [6]. For newly diagnosed anaplastic gliomas without 1p19q co-deletion, interim results of the CATNON trial, indicate that patients who receive radiation plus 12 cycles of adjuvant TMZ have improved survival compared with those who do not receive adjuvant TMZ [7]. Currently, there is an ongoing randomized trial of 1p19q co-deleted tumors comparing RT plus PCV (procarbazine, lomustine, vincristine) with RT plus TMZ ("CODEL") [8]. We are still waiting for better therapies of recurrent CNS tumors. The TAVAREC trial from the European Organization of Research and Treatment of Cancer (EORTC) showed that the addition of bevacizumab (BEV) to TMZ did not improve OS, PFS, or cognitive function in recurrent grade II and III 1p/19q intact gliomas; regardless of isocitrate dehydrogenase (IDH) mutational status [9]. EORTC 26101 did not demonstrate the addition of BEV to lomustine, benefiting patients with progressive glioblastoma [10]. CheckMate-143, a randomized Phase III clinical trial of nivolumab in patients with first recurrence of glioblastoma did not meet its primary endpoint of improved OS over BEV monotherapy [11]. The data were presented on May 7, 2017 at the World Federation of Neuro-Oncology Societies (WFNOS) meeting in Zurich, Switzerland. Tumor-treating fields (TTFields) are produced from a patient-operated home-use device which delivers 200 kHz alternating electrical field to the brain. The treatment interferes with cell divisions and selectively disrupts mitosis by interfering with spatial alignment of polar macro-molecules within the cell. It also inhibits the repair of double strand breaks. It is gaining momentum as a therapeutic approach for glioblastoma with high therapeutic index but minimal side effects. Stupp et al. reported the results of a phase III randomized trial of 695 patients comparing the use of maintenance TTFields with TMZ vs. TMZ alone in newly diagnosed glioblastoma: median PFS of 7.1 vs. 4.0 months and OS of 20.5 vs.15.6 months, respectively [12]. Guidelines from the American National Comprehensive Cancer Network (NCCN) and European Association of Neuro- Oncology (EANO) are very useful [13, 14]. Clinicians are encouraged to watch the NCCN, EORTC and EANO website for new guidelines or updates [15, 16]. The entire thematic issue attempts to cover most common CNS tumors. It will be of great teaching value for clinicians in practice or in training.

This thematic issue covers a different aspect of management for lung cancer. Lung cancer is the major cause of cancer mortality in men and women worldwide. The current role and recent advances of screening, imaging, staging, pathology [1], molecular markers, surgery, radiotherapy, systemic therapy, and palliative care are reviewed. The entire thematic issue has many illustrative clinical cases which will be of great teaching value for clinicians in practice or in training. Regarding lung cancer screening, the Cancer Care Ontario Guidelines [2] suggest using low-dose Computerized Tomography (CT) to screen asymptomatic patients between 55-74 years of age with at least a 30 pack-year smoking history who are current smokers or have quit within the previous 15 years. Beginning in 2018, the eighth edition of American Joint Commission on Cancer staging will be used [3]. The comparison can be seen in details in the overview by Davidson et al., In 2011, the International Association for the Study of Lung Cancer, American Thoracic Society, and European Respiratory Society (IASLC/ATS/ERS) proposed a modified lung adenocarcinoma classification [4]. Changes in the 2004 WHO Classification include the removal of the term “Bronchioloalveolar Carcinoma” (BAC) and the addition of the terms “Adenocarcinoma In Situ” (AIS) and “Minimally Invasive Adenocarcinoma” (MIA). Further changes are seen in the 2015 WHO Classification, in the overview by Davidson et al., [1]. Only resection specimen can diagnose adenocarcinoma in situ, not based on small biopsy or cytology in which the proper terminology is adenocarcinoma with lepidic pattern. Apart from lung cancer, mesotheliomas and thymomas are discussed in the overview of Lee, et al. An advanced large cell neuroendocrine carcinoma (stage III and IV) is treated like Extensive Stage Small Cell Lung Cancer (ESSCLC) by chemotherapy and then Prophylactic Cranial Irradiation (PCI) for responders [5]. Systematic reviews show that complex radiation technology with Image-Guided Radiotherapy (IGRT) improves the precision of radiation treatment and minimizes toxicity. The current standard of care for ES-SCLC recommends PCI for responders. The landmark EORTC study by Slotman et al., [6] had criticized that patients did not have baseline MRI. A randomized Japanese study of 169 patients mandated baseline MRI to rule out brain metastases before enrolment. The median follow-up was 9 months as the trial was stopped early due to futility. There was a trend towards inferior survival as the overall median survival rates were 10.1 and 15.1 months with and without PCI (P=0.091) [7]. Researchers from the University of Heidelberg studied 136 ES-SCLC patients. Baseline contrast CT or MRI head did not show any significant difference in survival [8]. Their results showed an overall survival benefit of PCI. Similarly, the 318 ES-SCLC patients in the North Central Cancer Treatment Group pooled analysis benefit from PCI. In the past, neurotoxicity of PCI could not be demonstrated but RTOG 2012 documented this at 12 months [9]. PCI is not recommended in patients with poor performance status, impaired neurocognitive function and is questioned in resected stage I small cell lung cancer and the elderly of 80 years old or more [10, 11]. Physicians tend to overestimate the life expectancy of cancer patients [12]. This leads to over-treatment of patients, and wasting resources. Early palliative care for metastatic non-small cell lung cancer patients is associated with less aggressive treatments, better quality of life, mood of patients/ caregivers, and longer survival (11.6 months vs. 8.9 months, P=0.02) [13]. Careful selection of patients for radical or palliative treatment is required. Different models are proposed to predict life expectancy of sick cancer patients in the overview of palliative care by Lee et al., To relieve respiratory symptoms, modern procedures include bronchoscopic stenting to establish airway patency, brachytherapy, electro-cautery or balloon bronchoplasty to control hemoptysis, or endoscopic debridement by cryosurgery, photo-resection to debulk tumors and heliox (combination of helium and oxygen) [14]. Expedited referral pathways, or rapid access program was first implemented in Vancouver, Canada. Researchers reported that, in retrospective comparison to their standard clinic, improved wait times, increased connections with supportive services, and more efficient clinical workload was achieved through their newer streamlined process. Their report specifically indicated a quicker median wait time from referral to the consultation of 7 days; with almost three-quarters receiving radiation treatment on the same day as their first consult, and with over half of the patients connected to an additional desired health service [15]. End of life issues e.g. euthanasia and medically assisted suicide are ethical controversial hot topics that many countries are debating. Wright et al. showed that end of life discussion resulted in less aggressive treatment, like intensive care unit admission [16]. Aggressive treatment is associated with worse quality of life of patient and caregiver bereavement adjustment. End of life care for lung cancer varies with different countries. In the present thematic issue, we have invited oncologists from Hong Kong, France and Canada to express their opinions about palliative and end of life care. These have been discussed in the last review of the thematic issue. We would like to acknowledge the diligent efforts of the authors, co-authors, reviewers, and support personnel for making the thematic issue possible.

No Text Found

No Text Found