Management options for follicular lymphoma: observe; R-CHOP; B-R; others?

Treatment results are improving for patients who have advanced-stage follicular lymphoma; this progress is in large part related to the inclusion of anti-CD20 monoclonal antibody therapy in front-line therapy programs. Rituximab has been combined successfully in chemo-immunotherapy regimens with several standard chemotherapy combinations, and with bendamustine. Post-remission treatment strategies, including radioimmuotherapy consolidation and rituximab maintenance, have had a favorable impact on duration of remission. Thus, although traditional palliative strategies can still have a role in many situations, such approaches must now be placed in perspective with options that have the potential to achieve durable disease control. Recent therapeutic advances have renewed the hope that potentially curative treatment options may be forthcoming for these patients.     

Ablative radiosurgery for cardiac arrhythmias – A systematic review

Stereotactic body radiotherapy (SBRT) is a high precision technique that is commonly used for malignant lesions in lung, liver, pancreas and spine. Recent reports suggest promise in use of SBRT as a tool in atrial and ventricular cardiac arrhythmias. The present systematic review deals with the use of SBRT technology for this novel indication. A PubMed search was done for articles published between 1990 and 2020. All original articles, case reports, case series of treated patients were included in the analyses. Out of the 55 articles in PubMed search, our search found 1 phase I/II clinical case series, 3 clinical case reports, 3 animal studies and 4 dosimetric studies related to cardiac SBRT for arrythmias. All studies used a uniform cardiac dose of 25 Gy. The available preclinical, dosimetric and clinical studies have suggested that SBRT for cardiac arrhythmias could become a potential alternative in suitable patients. Cardiac and radiation oncology community await further data and experience in this modality, including safety and outcomes.     

Systemic therapy for early‐stage HER2‐positive breast cancers: Time for a less‐is‐more approach?

Trastuzumab‐based chemotherapy has dramatically improved outcomes for patients with all stages of human epidermal growth factor receptor 2 (HER2)‐positive breast cancer. Additional HER2‐directed agents that have recently been approved are also expected to improve outcomes. Patients with small, lymph node‐negative, HER2‐positive breast cancers who are treated with trastuzumab‐based chemotherapy demonstrate especially favorable responses, with 5‐year recurrence rates of <5%. In this review, recent data regarding response rates among patients with early‐stage HER2‐positive breast cancer treated with trastuzumab‐based chemotherapy are discussed. This review supports future studies of the possible omission of chemotherapy in a subset of patients with HER2‐positive cancers, specifically those that coexpress hormone receptors. Cancer 2015;121:517–526. © 2014 American Cancer Society.     

Is there a “mucosa-sparing” benefit of IMRT for head-and-neck cancer?

PURPOSE: To investigate whether intensity-modulated radiation therapy (IMRT) allows more mucosal sparing than standard three-field technique (3FT) radiotherapy for early oropharyngeal cancer. METHODS AND MATERIALS: Whole-field IMRT plans were generated for 5 patients with early-stage oropharyngeal cancer according to Radiation Therapy Oncology Group 0022 (66 Gy/30 fractions/6 weeks) guidelines with and without a dose objective on the portion of mucosa not overlapping any PTV. 3FT plans were also generated for the same 5 patients with two fractionation schedules: conventional fractionation (CF) to 70 Gy/35 fractions/7 weeks and concomitant boost (CB) to 72 Gy/40 fractions/6 weeks. Cumulative dose volume histograms (DVHs) of the overall mucosal volume (as per in-house definition) from all trials were compared after transformation into the linear quadratic equivalent dose at 2 Gy per fraction with a time factor correction. RESULTS: Compared with IMRT without dose objective on the mucosa, a 30-Gy maximum dose objective on the mucosa allows approximately 20% and approximately 12% mean absolute reduction in the percentage of mucosa volume exposed to a dose equivalent to 30 Gy (p < 0.01) and 70 Gy (p < 0.01) at 2 Gy in 3 and 7 weeks, respectively, without detrimental effect on the coverage of other regions of interest. Without mucosal dose objective, IMRT is associated with a larger amount of mucosa exposed to clinically relevant doses compared with both concomitant boost and conventional fractionation; however, if a dose objective is placed, the reverse is true, with up to approximately 30% reduction in the volume of the mucosa in the high-dose region compared with both concomitant boost and conventional fractionation (p < 0.01). CONCLUSIONS: Intensity-modulated radiation therapy can be potentially provide more mucosal sparing than traditional approaches.     

Screening for Colorectal Cancer Leading into a New Decade: The “Roaring ‘20s” for Epigenetic Biomarkers?

Colorectal cancer (CRC) has an important bearing (top five) on cancer incidence and mortality in the world. The etiology of sporadic CRC is related to the accumulation of genetic and epigenetic alterations that result in the appearance of cancer hallmarks such as abnormal proliferation, evasion of immune destruction, resistance to apoptosis, replicative immortality, and others, contributing to cancer promotion, invasion, and metastasis. It is estimated that, each year, at least four million people are diagnosed with CRC in the world. Depending on CRC staging at diagnosis, many of these patients die, as CRC is in the top four causes of cancer death in the world. New and improved screening tests for CRC are needed to detect the disease at an early stage and adopt patient management strategies to decrease the death toll. The three pillars of CRC screening are endoscopy, radiological imaging, and molecular assays. Endoscopic procedures comprise traditional colonoscopy, and more recently, capsule-based endoscopy. The main imaging modality remains Computed Tomography (CT) of the colon. Molecular approaches continue to grow in the diversity of biomarkers and the sophistication of the technologies deployed to detect them. What started with simple fecal occult blood tests has expanded to an armamentarium, including mutation detection and identification of aberrant epigenetic signatures known to be oncogenic. Biomarker-based screening methods have critical advantages and are likely to eclipse the classical modalities of imaging and endoscopy in the future. For example, imaging methods are costly and require highly specialized medical personnel. In the case of endoscopy, their invasiveness limits compliance from large swaths of the population, especially those with average CRC risk. Beyond mere discomfort and fear, there are legitimate iatrogenic concerns associated with endoscopy. The risks of perforation and infection make endoscopy best suited for a confirmatory role in cases where there are positive results from other diagnostic tests. Biomarker-based screening methods are largely non-invasive and are growing in scope. Epigenetic biomarkers, in particular, can be detected in feces and blood, are less invasive to the average-risk patient, detect early-stage CRC, and have a demonstrably superior patient follow-up. Given the heterogeneity of CRC as it evolves, optimal screening may require a battery of blood and stool tests, where each can leverage different pathways perturbed during carcinogenesis. What follows is a comprehensive, systematic review of the literature pertaining to the screening and diagnostic protocols used in CRC. Relevant articles were retrieved from the PubMed database using keywords including: “Screening”, “Diagnosis”, and “Biomarkers for CRC”. American and European clinical trials in progress were included as well.     

Liposome-coated lipoplex–based carrier for antisense oligonucleotides

The chemical nature of genetic drugs (e.g. antisense oligonucleotides, siRNA, vectors) requires a suitable carrier system to protect them from enzymatic degradation without changing their properties and enable efficient delivery into target cells. Lipid vectors for nucleic acid delivery that have been widely investigated for years can be very effective. As the majority of attempts made in the field of cancer gene therapy have focused on solid tumors, while blood cancer cells have attracted less attention, the latter became the subject of our investigation. The lipid carrier proposed here is based on liposomes constructed by others but the lipid composition is original. A liposome-coated lipoplex (L-cL) consists of a core arising from complexation of positively charged lipid and negatively charged oligodeoxynucleotide (ODN) or plasmid DNA coated by a neutral or anionic lipid bilayer. Moreover, our lipid vector demonstrates size stability and is able to retain a high content of enclosed plasmid DNA or antisense oligodeoxynucleotides (asODNs). Observed transfection efficacies of the tested preparation using a plasmid coding for fluorescent protein were up to 60-85% of examined leukemia cells (Jurkat T and HL-60 lines) in the absence or the presence of serum. When BCL‑2 asODN was encapsulated in the L-cL, specific silencing of this gene product at both the mRNA and protein level and also a markedly decreased cell survival rate were observed in vitro. Moreover, biodistribution analysis in mice indicates prolonged circulation characteristic for PEG-modified liposomal carriers. Experiments on tumor-engrafted animals indicate substantial inhibition of tumor growth.     

End-of-life care for glioma patients; the caregivers’ perspective

Journal of Neuro-Oncology - Gliomas are primary brain tumors with a life-limiting course of disease, and the last weeks of life are often characterized by neurological deficits that affect...     

Strontium‐89 treatment for prostate cancer bone metastases: Does a prostate‐specific antigen response predict for improved survival?

A review of 50 patients treated with strontium‐89 for prostate cancer bone metastases from January 1993–1997 at the Wellington Cancer Centre was undertaken to determine if there was any correlation between changes in prostate‐specific antigen (PSA) following treatment and subsequent survival. Thirty cases were evaluable for PSA response. Of these, 14 had a fall in PSA following strontium‐89 treatment, and their mean survival was 641 days. The remaining 16 patients did not demonstrate a post‐treatment fall in PSA and their mean survival was 275 days. A difference between these two groups in the time to development of new bone symptoms following treatment was also observed. No significant correlation between pretreatment PSA and PSA response was observed. In conclusion, a PSA response following strontium‐89 treatment appears to predict for improved survival in patients with bone metastases from carcinoma of the prostate. Further prospective studies are indicated.     

Surgical and ablative therapies for the management of adrenal ‘oligometastases’ – A systematic review

Background

We systematically reviewed the literature on the use of surgery, stereotactic ablative body radiotherapy (SABR) and percutaneous catheter ablation (PCA) techniques for the treatment of adrenal metastases to develop evidence-based recommendations.

Methods

A systematic review of the MEDLINE database was performed using structured search terms following PRISMA guidelines. Eligible publications were those published from 1990 to 2012, written in English, had at least five patients treated for adrenal metastasis and reported on patient clinical outcomes (local control, survival and treatment related complications/toxicity). Where possible, pooled 2-year local control and overall survival outcomes were analysed.

Results

Our search strategy produced a total of 45 papers addressing the three modalities – 30 adrenalectomy, nine SABR and six PCA (818, 178 and 51 patients, respectively). There was marked heterogeneity in outcome reporting, patient selection and follow-up periods between studies. The weighted 2-year local control and overall survival for adrenalectomy were 84% and 46%, respectively, compared with 63% and 19%, respectively for the SABR cohort. Only one study of PCA with five patients analysed clinical outcomes, reporting an actuarial local control of 80% at 1 year. Treatment related complications/toxicities were inconsistently reported.

Conclusion

There is insufficient evidence to determine the best local treatment modality for isolated or limited adrenal metastases from any primary tumour. Published data suggests adrenalectomy to be a reasonable treatment approach for isolated adrenal metastasis in suitable patients. SABR is a valid alternative in cases when surgery is not feasible or the operative risk is unacceptable. PCA cannot be recommended until there are more robust studies which include long-term oncological outcomes.     

Low‐lying placenta: Who should be recalled for a follow‐up scan?

Introduction: The incidence of low‐lying placenta or placenta praevia in the second trimester has been reported at 1–5%; however, recent unpublished audits suggest our recall rates are higher. We wanted to assess our recall rates in a large sample size and determine whether we could reduce the placenta–os distance for recalling women with low‐lying placenta, while still identifying all cases of placenta praevia at delivery. Methods: We undertook a retrospective analysis from March 2005 to March 2008 of women attending for 18–20‐week obstetric ultrasounds. Patients with a singleton pregnancy and a placenta ≤2 cm from the internal cervical os were included. Follow‐up scan results and delivery data were collected. Results: Four hundred eight women were identified as having a low‐lying placenta at the 18–20‐week scan (107 (9%) at Dunedin Hospital and 301 (5%) at Otago Radiology). Fifty‐eight women (14%) were excluded, leaving 350 women included in the analysis. Three hundred seventeen (91%) had a placenta clear of the internal os on their follow‐up scan while 33 women (9%) had persistent placenta praevia. At a distance of ≥1.9 cm, there was 100% sensitivity for detection of placenta praevia on the 18–20‐week scan. As the placenta–os distance decreases the sensitivity for detection of placenta praevia reduces. Conclusions: Placenta praevia at term can occur where the placenta is up to 1.9 cm from the internal cervical os on the 18–20‐week anatomy scan. Consequently, we will continue to recall women for a follow‐up scan where the placenta is ≤2 cm from the internal os.