Radiation Therapy for Liver Tumors: Ready for Inclusion in Guidelines?

Despite the historically limited role of radiotherapy in the management of primary hepatic malignancies, modern advances in treatment design and delivery have renewed enthusiasm for radiation as a potentially curative treatment modality. Surgical resection and/or liver transplantation are traditionally regarded as the most effective forms of therapy, although the majority of patients with hepatocellular carcinoma and intrahepatic cholangiocarcinoma present with locally advanced or unresectable disease on the basis of local vascular invasion or inadequate baseline hepatobiliary function. In this context, many efforts have focused on nonoperative treatment approaches including novel systemic therapies, transarterial chemoembolization, ethanol ablation, radiofrequency ablation, and stereotactic body radiation therapy (SBRT). This review aims to summarize modern advances in radiotherapy, particularly SBRT, in the treatment of primary hepatic malignancies.     

Predictive signatures for chemotherapy sensitivity in breast cancer: Are they ready for use in the clinic?

Markers that predict the sensitivity of tumours to chemotherapy must address two questions: (a) which tumours are more likely to respond to chemotherapy? and (b) what is the optimal chemotherapy regimen for a specific tumour or group of tumours? To answer these questions will require markers of general chemosensitivity and drug-specific chemosensitivity, respectively. Beyond these fundamental questions lies an important practical question: are the predictive markers in the current literature ready for routine clinical use? The focus of this paper is to address this practical question. We will first review retrospective trials that have reported promising chemotherapy signatures, presenting in a comprehensive manner for the non bio-informatician the different methods used so far. In addition, we will summarise prospective trials (either ongoing or under development) designed to test the multigene classifiers currently thought to predict chemosensitivity. Finally, we will discuss why microarray studies have so far failed to identify new targets, and how we might be able to improve on these results through large-scale genotyping of tumours.     

Retention of paclitaxel in cancer cells for 1 week in vivo and in vitro

Purpose: Clinically, the administration of paclitaxel for ovarian cancer on a dose-dense weekly schedule, rather than the conventional every-3-week schedule, might demonstrate greater tumor-cell death. Here, we investigate the pharmacokinetics and the pharmacodynamics of weekly paclitaxel in cancer cells in vivo and in vitro. Experimental design: Paclitaxel concentrations were measured by HPLC, and apoptotic cells were detected by TUNEL assay in paclitaxel-pretreated cervical cancer cells treated with paclitaxel (10 ng/ml) and in the tissues of cervical cancer patients treated with weekly paclitaxel (60 mg/m²/week). Polymerized tubulin was detected with a tubulin polymerization assay, and the BrdU cell proliferation assay was used to assess the effect of paclitaxel. Results: Paclitaxel remained in the cancer tissues of six patients for 6 days after the last medication. In vitro, paclitaxel was retained in all cell lines for 24 h after its removal from the medium, and paclitaxel was still detectable in CaSki cells on day 7. Simultaneous treatment with depolymerizing drugs inhibited the retention of paclitaxel in cells and paclitaxel-induced polymerization of tubulin. After paclitaxel treatment, apoptotic cells were detected in cancer tissues and CaSki cells for 1 week. Under high magnification, apoptotic cells on day 7 after paclitaxel treatment showed multinucleation. Conclusions: Paclitaxel is unusual in that it accumulates especially in cancer cells and induces apoptosis for 1 week in vivo and in vitro. On the other hand, paclitaxel could not be detected in cancer tissues after 2 weeks. The administration of paclitaxel on a weekly schedule, rather than the standard every-3-week schedule, might produce greater tumor-cell death.     

Stopping a trial early in oncology: for patients or for industry?

We read the article by Trotta et al. [1] with interest and agreethat reporting of randomized controlled trials (RCTs) beforemeeting protocol-defined criteria for conducting a final analysisis an important and complex issue. However, we differ from someof their conclusions. The authors analyzed 25 RCTs that were reported from 1997 to2007 that were selected for review based on     

Is chronic sunlight exposure important in accounting for increases in melanoma incidence?

Most attempts to relate changes in patterns of sunlight exposure to the rise in incidence of malignant melanoma have concentrated on the positive association between intermittent exposure to sunlight and risk of melanoma. The Western Canada Melanoma Study, however, also detected a significant inverse association between melanoma and chronic or long-term occupational sun exposure in men, with the lowest risk (OR = 0.5) in those with maximum occupational exposure, suggesting that chronic exposure may be protective. Data obtained from Canadian census figures indicated that since 1951 there has been a substantial reduction in the number of males engaged in outdoor occupations in Canadian society. These observations suggest that part of the increase in the incidence of melanoma in low-sunlight areas may be due to a reduction over the past 40 years of the size of this group of individuals "protected" by their exposure to UV light.     

Experience with curative radiotherapy for cervix cancer in the Bahamas for 2006–2016

Background

Cervix cancer is a significant health problem. As access to quality care in Small Island Developing States improves, and cancer centers become established, providers of care can summarize local experience to benchmark system quality and look for ways to further improve value.

Methods

This is a retrospective study of all cases of cervix cancer managed 2006–2016 at The Cancer Centre Bahamas, in conjunction with Princess Margaret Hospital, Nassau, affiliated with The University of West Indies. Seventy-two women received curative radiotherapy or chemoradiotherapy. Herein are reported presenting characteristics, treatments, waiting and overall treatment times, plus outcomes of recurrence, survival, and adverse events.

Results

For 68 newly diagnosed cases, median waiting time (diagnosis to commencing treatment) was 110 days. It was 90 days for those 47 cases who had no prior surgery or neoadjuvant chemotherapy. Overall, 99% of intended external radiotherapy fractions, 74% of brachytherapy sessions, and 79% of concurrent weekly chemotherapy were administered. For all 72 cases, median overall treatment time was 63 days; and for the 47 case sub-group, it was 78 days during 2006–2010 and 65 days during 2011–2016 (p?=?0.005), so improving over calendar time. Four cases experienced grade 3–4 toxicities. Twelve had urological complications from disease or treatment. Five cases experienced local failure; eight experienced distant failure. Newly diagnosed stage 2B (26/72) had a 2-year survival of 71%.

Conclusion

This report demonstrates the impact of providing curative radiation-based treatments for cervical cancer in a small state. It suggests ways to further improve operations and justifies additional research.

     

Reasons for Patient’s Delay in Diagnosis of Breast Carcinoma in Pakistan

Background: Delay in diagnosis of breast cancer is associated with a poorer survival and a pivotal contributionto this delayed diagnosis comes from patient delay in presenting at a clinic. Reasons involved must be evaluatedin order to decrease this reducible delay. Objectives: i) To evaluate the reasons for patient delay in diagnosis ofbreast cancer; ii) to investigate any association with other variables. Materials and Methods: A 6 month crosssectional study (from July 2012 to Dec 2012), was carried out in Surgical and Oncology Units of Civil Hospital,Karachi. A total of 100 females diagnosed with breast cancer of any histological type were interviewed afterinformed consent and relevant data were collected. Due ethical clearance was obtained. Results: Mean age was47.5±12.1 years with a range from 25-77 years. Mean duration of delay was 5.13±4.8 months, from shortest 1month to longest 36 months. Duration of delay was observed to be no delay (<1 month) in 28%, short delay (1-3months) in 30% and long delay (>3 months) in 42% of patients. Considering the symptoms as “harmless” (39%)was the most frequent reason of delay followed by “temporary” (20%) and the “use of traditional methods”(12%). Most common reason for later approaches was an increase in the size of the lump (41%). Statisticallysignificant association (p-value <0.05) of longer patient delay was obtained with being single, being illiterate,painless breast lump as the first symptom, negative family history of breast cancer and vague attribution of thesymptoms. Conclusions: Significant delay in approach to health care facility was observed in our study due tovariable reasons given by women. Sufficient awareness regarding breast cancer, its symptoms and favorableeffects of a timely diagnosis on prognosis must be imparted to our general population.     

Is there still a role for surgery in esophageal carcinoma in 2007?

Regarding curative treatment of oesophageal carcinoma, many therapeutic options could be planned. Surgery is traditionally considered as the most appropriate treatment for locoregional control and long-term survival. Because of the poor prognosis, muldisciplinary approach is necessary, including surgery, radiotherapy and chemotherapy, alone or in association. However, because of the small number of well randomised trials, the question of which treatment is the most appropriate is still under debate. In 2007, following therapeutic strategies could be drawn: surgery is the main treatment, used alone for stages I and IIa, in association with neoadjuvant chemotherapy (CT) or chemoradiation (CRT) for stages IIb. For locally advanced tumours (stage III), adenocarcinomas required neoadjuvant CT or CRT followed by surgery, whereas for squamous cell carcinomas exclusive CRT is the main treatment with following important conditions : (i) response to CRT, (ii) curative salvage surgery in case of non response after 2 cycles or persistent tumour after 4 cycles, (iii) long-term survival may be probably enhanced by adjuvant surgery in experienced centres for selected patients.     

What and Where for Publications by Cancer Registries in the Asian Pacific? - Roles for the APJCP in the Future

The absolute necessity of cancer registration for cancer control planning is well accepted. The registry at thenational or local level can provide not only essential data for cancer incidence, mortality and survival but mayalso point to risk and protective factors and efficacy of interventions by conducting epidemiological research.Timely publication of research findings in PubMed indexed journals is of the essence, especially in examplesthat allow free access so that the widest dissemination of information can be achieved. The present commentarycovers the scope of research in Asia or using Asian data the period 2008-2013, nearly 40% of a total of over 300papers being published in the APJCP. In order to reach its full potential the registry should incorporate manyskills. Cooperation for this purpose, whether it be national, regional, Asia-wide or international, is a high priorityand the International Agency for Research on Cancer, together with the National Cancer Institute in Thailandand the APOCP/APJCP are staging an Asian Cancer Network Forum in Bangkok in February of 2014 to allowdiscussion of ways forward. It is hoped that representatives from all regions of Asia will decide to attend anda l so contribute country reports for publication in a special supplement of the APJCP.     

Are there indications for chemotherapy in hepatocellular carcinoma?

Single-agent Adriamycin gives a response rate of around 15% to 20%, and with combination therapy, this figure rises to around 20% to 35%; however, there is no proven survival benefit. Nonetheless, HCC is clearly not entirely chemotherapy resistant and complete pathologic remission is possible after systemic combination chemotherapy alone. Major methodologic problems remain in assessment of response and the survival benefit from systemic therapy. Until these are resolved, the answer to the question posed in this article is unknown; further appropriate studies remain to be undertaken.     

New developments in immunotherapy for non-Hodgkin’s lymphoma

The clinical development of immunotherapy with rituximab (chimeric anti-CD20 monoclonal antibody) has markedly affected the treatment approach for patients with B-cell non-Hodgkin’s lymphoma (NHL). Rituximab was initially evaluated in relapsed indolent lymphoma and has substantial activity in this setting both alone and in combination with chemotherapy. Ongoing efforts in indolent NHL are seeking to optimize the dose and schedule of rituximab through ‘maintenance’ strategies exploring chemotherapyrituximab combinations and the use of other biologic agents or antibodies that may enhance activity when employed together with rituximab. Other studies in indolent NHL suggest that radiolabeled anti-CD20 antibodies (such as I-131 tositumomab and Y-90 ibritumomab tiuxetan) may be useful in relapsed and refractory disease and have potential utility as part of initial treatment as well. In diffuse large B-cell lymphoma, the addition of rituximab to CHOP chemotherapy can improve survival, though benefits are more limited in mantle cell lymphoma. Further studies of unlabeled and radiolabeled immunotherapies are ongoing in order to optimize their use for maximal clinical benefit.     

Time for more optimism in metastatic breast cancer?

Treatment of metastatic breast cancer has substantially changed in the last decades. Availability of new cytotoxics and targeted therapies as well as changes in treatment philosophy and strategy have all contributed to a significant improvement in both survival and patients’ quality of life. The multidisciplinary approach, personalised treatments based on tumour characteristics, patient’s and disease history, as well as re-definition of treatment goals, aiming at the lowest possible impact on patients’ life by replacing aggressive multidrug chemotherapy with single-agent cytotoxic treatment or endocrine ± targeted therapies, have all been the bases of the new treatment paradigm. More recently the development of the international advanced breast cancer (ABC) consensus guidelines have further contributed to this improvement. This review will focus on the major achievements and challenges in the different tumour subtypes and sites, with a focus on future research topics and trends.     

Catheter-related Complications in Postoperative Intraperitoneal Chemotherapy for Gastric Cancer

Objective： To analyze catheter-related complications during postoperative Intraperitoneal chemotherapy （IPCT） for gastric cancer. Methods： From December 2003 to April 2007, 80 patients with gastric cancer were treated with postoperative IPCT using central venous catheters （CVCs）, during which the complications that occurred in association with CVCs were documented and analyzed. Results： Catheter-related complications were seen in 10 out of the 80 patients, yielding a total complication rate of 12.5%. Main complications included abdominal pain （3.8%）, local infection （1.3%）, catheter obstruction （2.5%）, leakage （2.5%） and dislocation （2.5%）. All patients successfully finished their IPCT, the success rate was 100%. There occurred no severe complications or treatment-related deaths. Conclusion： It is convenient and safe to carry out postoperative IPCT for gastric cancer using CVCs, which, with a low catheter-related complication rate, should be recommended for more clinic use.