A framework for rehabilitation for cancer survivors

This paper introduces a theoretical framework that recognises the rehabilitation needs of people who have cancer and offers a multi‐tiered model to meet these needs. Various models for providing survivorship care have been previously proposed, giving rise to multiple possible delivery systems. Existing cancer rehabilitation frameworks recognise different phases of illness, goals of care and the need for services at all stages of illness. The ‘Stained Glass Cancer Rehabilitation Framework’ incorporates survivor needs and rehabilitation modalities, arranged in a practical hierarchy and builds on earlier models. A broad view of rehabilitation services considers complexity, temporal and geographic factors. Recognition that needs emerge over time demands a routine long‐term approach to screening for physical, functional and psychosocial rehabilitation needs by medical and other health professionals. New methods of care delivery and coordination from specialist to primary care settings are needed, long after treatment is completed. Service delivery infrastructure supported by funding reform and training of rehabilitation professionals in delivering appropriate interventions for cancer survivors is essential, together with more research into cancer rehabilitation interventions, functional outcomes and their delivery.     

New paradigms for therapy for osteosarcoma

Osteosarcoma is a primary bone malignancy generally affecting the young, with 60% of cases occurring before the age of 25 years and the peak incidence at 15 years. Survival has improved over the past several decades, with nonmetastatic disease having an approximately 70% chance of long-term survival. Unfortunately, patients with metastatic disease at diagnosis or those who have recurrent disease have a dismal prognosis, with approximately 20% surviving long term. In this review article we describe several new therapies in development for osteosarcoma. These include immune-based therapies, strategies to inhibit tumor growth, radiotherapy, and the introduction of new chemotherapies and targets.     

Requirements for a treatment planning system for radioimmunotherapy

Cancer-seeking antibodies carrying radionuclides can, in theory, be very powerful agents for the radiotherapy of cancer. However, as with all radiotherapy, the undesired dose to critical normal organs is the limiting factor that determines success or failure. The distribution of radiation dose in cancer and noncancer tissue is highly dependent on choices the therapist can make: choices of the antigens to be targeted, choices of the antibodies or antibody fragments to be used, choices of radionuclides, of amounts, of timing, and other electives. New technologies, especially of monoclonal antibody production, make the options myriad. Optimization of this therapy depends on a foreknowledge of the radiation dose distributions to be expected. The necessary data can be acquired by established tracer techniques, in individual patients, for particular treatment selections. These tracer techniques can now be implemented by advanced equipment for quantitative, tomographic radionuclide imaging and strengthened by dynamic modeling of the physiological parameters which govern radionuclide distribution, and hence radiation dose distribution.     

Advocating for prehabilitation for patients undergoing gynecology-oncology surgery

Implementation of Enhanced Recovery After Surgery (ERAS) protocols in gynecology-oncology has resulted in improved perioperative outcomes. However, ERAS does not include preoperative interventions to address the comorbidities, malnutrition, weight loss/obesity, decreased functional capacity and high degree of anxiety and depression that are present in the gynecology-oncology patients. The amalgamation of these risk factors with the surgical stress response and chemoradiotherapy-related toxicities is associated with worse postoperative functional capacity and impaired quality of life. Not surprisingly, surgical-related decline in physical fitness is one of the most distressing symptoms reported by cancer patients. Restoring pre-treatment physical status and accelerating recovery can be done through prehabilitation. Prehabilitation is a multimodal program combining exercise, nutrition and psychological interventions to strengthen patients physically and mentally before surgery by addressing modifiable risk factors during the preoperative period thereby filling this existing gap. It has shown promising results in the colorectal and thoracic surgery populations. This paper elaborates on risk factors specific to the gynecology-oncology population, highlights selection criteria that should prompt referral to a prehabilitation program and advocates for the implementation of these programs in this population.     

Industry gains incentives for drugs for children

Under the FDA Safety and Innovation Act, manufacturers who get a drug for a rare pediatric disease approved and on the market earn a voucher requiring the FDA to review a second drug within 6 months of submission of an application for its approval.     

Radiometals as payloads for radioimmunotherapy for lymphoma

Because of their remarkable effectiveness in radioimmunotherapy (RIT), 2 anti-CD20 monoclonal antibody (MAb) drugs, one labeled with indium 111 for imaging or yttrium 90 for therapy, and another labeled with iodine I 131 for imaging and therapy, have been approved for use in patients with non-Hodgkin's lymphoma (NHL). Successful RIT for lymphomas is due in large part to the rapid and efficient binding of the targeted MAb to lymphoma cells. Carcinomas are more difficult to access, necessitating novel strategies matched with radionuclides with specific physical properties. Because there are many radionuclides from which to choose, a systematic approach is required to select those preferred for a specific application. Thus far, radionuclides with g emissions for imaging and particulate emissions for therapy have been investigated. Radionuclides of iodine were the first to be used for RIT. Many conventionally radioiodinated MAbs are degraded after endocytosis by target cells, releasing radioiodinated peptides and amino acids. In contrast, radiometals have been shown to have residualizing properties, advantageous when the MAb is localized in malignant tissue. b-emitting lanthanides like those of 90Y, lutetium 177, etc. have attractive combinations of biologic, physical, radiochemical, production, economic, and radiation safety characteristics. Other radiometals, such as copper-67 and copper-64, are also of interest. a-emitters, including actinium-225 and bismuth-213, have been used for therapy in selected applications. Evidence for the impact of the radionuclide is provided by data from the randomized pivotal phase III trial of 90Y ibritumomab tiuxetan (Zevalin) in patients with NHL; responses were about 2 times greater in the 90Y ibritumomab tiuxetan arm than in the rituximab arm. It is clear that RIT has emerged as a safe and efficient method for treatment of NHL, especially in specific settings.     

Follow-up for women after treatment for cervical cancer

Question

What is the most appropriate follow-up strategy for patients with cervical cancer who are clinically disease-free after receiving primary treatment?

Perspectives

For women with cervical cancer who have been treated with curative intent, follow-up includes identification of complications related to treatment and intervention in the event of recurrent disease. Most women who recur with cervical cancer are not curable; however, early identification of recurrence can alter disease management or treatment-planning options, and for those with a central pelvic recurrence and no evidence of distant disease, there is a potential for cure with additional therapy. Follow-up protocols in this population are variable, using a number of tests at a variety of intervals with questionable outcomes.

Outcomes

Outcomes of interest included recurrence, survival, and quality of life.

Methodology

The Gynecology Cancer Disease Site Group (dsg) conducted a systematic review of the literature and a narrative review of emerging clinical issues to inform the most appropriate follow-up strategy for patients with cervical cancer. The evidence was insufficient to specify a clinically useful recommended follow-up schedule, and therefore, the expert consensus opinion of the Gynecology Cancer dsg was used to develop recommendations on patient surveillance. The resulting recommendations were reviewed and approved by the Gynecology Cancer dsg and by the Program in Evidence-Based Care Report Approval Panel. An external review by Ontario practitioners completed the final phase of the review process. Feedback from all parties was incorporated to create the final practice guideline.

Results

The systematic review of the literature identified seventeen retrospective studies. The Gynecology Cancer dsg used a consensus process to develop recommendations based on the available evidence from the systematic review, the narrative review, and the collective clinical experience and judgment of the dsg members.

Practice Guideline

The recommendations in this practice guideline are based on the expert consensus opinion of the Gynecology Cancer dsg, informed by evidence from retrospective studies. These are some general features of an appropriate follow-up strategy:

1. At a minimum, follow-up visits with a complete physical examination, including a pelvic–rectal exam and a patient history, should be conducted by a physician experienced in the surveillance of cancer patients.
2. There is little evidence to suggest that vaginal vault cytology adds significantly to the clinical exam in detecting early disease recurrence.
3. Routine use of various other radiologic or biologic follow-up investigations in asymptomatic patients is not advocated, because the role of those investigations has yet to be evaluated in a definitive manner.
4. A reasonable follow-up schedule involves follow-up visits every 3–4 months in the first 2 years and every 6–12 months in years 3–5. Patients should return to annual population-based general physical and pelvic examinations after 5 years of recurrence-free follow-up.

     

Technique for external beam treatment for mesothelioma

A combined photon-electron beam treatment for diffuse pleural mesothelioma is discussed in this paper. The technique consists of parallel opposed 10 MV X rays prescribed to 4250 cGy using customized blocks to shield the lung. The pleura is then boosted with electrons to a dose of 3600 cGy. The combination yields a TDF of 74 ret to the pleura. As discussed in an earlier paper, this treatment method when combined with subtotal pleurectomy and I-125 implantation leads to improved survivals with minimal complications. The details of this 3-dimensional radiation treatment method were not described in detail. To improve target coverage and local control, the technique has been modified. CT is now used along with simulation plane films to define the entire pleural surface. The target volume has also been extended from the dome to the base of this diaphragm. These changes have led to improved pleural dose distributions; by blocking the liver or stomach, and boosting the crus of the diaphragm with electrons, there is little added morbidity. As is demonstrated by dose volume histograms, we have been able to deliver 4250 cGy +/- 10% to most of the pleura with 1/3 of the lung parenchyma receiving less than 2100 cGy.     

Criteria for the selection of radionuclides for targeting nuclear antigens for cancer radioimmunotherapy

The potential of utilizing immunoconjugates to selectively deliver radionuclides for the destruction of tumors has stimulated much research activity. From dosimetric and other considerations, the choice of radiolabel is an important factor that needs to be optimized for maximum effectiveness of radioimmunotherapy (RIT). This paper reviews and assesses a number of present and future radionuclides that are particularly suitable for RIT based on the various physical, chemical, and biological considerations. Although intermediate to high-energy beta emitters (with and without gamma photons in their emission) possess a number of advantages for most RIT, the use of alpha, Auger, and short range conversion electron emitters could be attractive for targeting nuclear antigens when the radioimmunoconjugate is internalized into tumor cells. Factors relating to the production and availability of candidate radionuclides as well as their stable chemical attachment to monoclonal antibodies are discussed.     

Strategies for screening for pancreatic adenocarcinoma in high-risk patients

Screening high-risk individuals with imaging tests, such as endoscopic ultrasound and computed tomography, can lead to the detection and treatment of predominantly asymptomatic premalignant lesions. These pancreatic lesions consist of resectable, mostly branch-type non-invasive intraductal papillary mucinous neoplasms. Endoscopic ultrasound features of chronic pancreatitis are highly prevalent in high-risk individuals and these directly correlate with multifocal lobulocentric parenchymal atrophy due to pancreatic intraepithelial neoplasia. Long-term, multi-prospective studies are needed to determine if screening for early pancreatic adenocarcinoma and timely intervention will result in decreased pancreatic cancer incidence and mortality in high-risk individuals.     

Basis for molecular diagnostics and immunotherapy for esophageal cancer

Introduction: Esophageal cancer (EC) is an extremely aggressive neoplasm, diagnosed in about 17,000 Americans every year with a mortality rate of more than 80% within five years and a median overall survival of just 13 months. For decades, the go-to regimen for esophageal cancer patients has been the use of taxane and platinum-based chemotherapy regimens, which has yielded the field’s most dire survival statistics.

Areas covered: Combination immunotherapy and a more robust molecular diagnostic platform for esophageal tumors could improve patient management strategies and potentially extend lives beyond the current survival figures. Analyzing a panel of biomarkers including those affiliated with taxane and platinum resistance (ERCC1 and TUBB3) as well as immunotherapy effectiveness (PD-L1) would provide oncologists more information on how to optimize first-line therapy for EC.

Expert commentary: Of the 12 FDA-approved therapies in EC, zero target the genome. A majority of the approved drugs either target or are effected by proteomic expression. Therefore, a broader understanding of diagnostic biomarkers could give more clarity and direction in treating esophageal cancer in concert with a greater use of immunotherapy.