NEWS FROM THE WORLD OF ONCOLOGY
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|Year : 2019 | Volume
| Issue : 3 | Page : 287--289
News from the world of oncology
|How to cite this article:|
. News from the world of oncology.Indian J Cancer 2019;56:287-289
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. News from the world of oncology. Indian J Cancer [serial online] 2019 [cited 2020 Feb 25 ];56:287-289
Available from: http://www.indianjcancer.com/text.asp?2019/56/3/287/263042
Benefits of Early Palliative Care Referral in Pancreatic Cancer
Pancreatic cancer is not uncommon and the median overall survival of locally advanced or metastatic pancreatic cancer is approximately 12 months. Late presentation is common and therapy is only modestly effective. Palliative care aims to improve quality of life and can very easily be coupled with any standard cancer treatment option. Although the World Health Organisation and the American Society of Clinical Oncology guidelines for metastatic pancreatic cancer recommends early initiation of palliative care, it has usually been offered at the end-of-life (EOL) stage. In a recent study from Australia by Natasha Michael et al. titled “Timing of palliative care referral and aggressive cancer care toward the end-of-life in pancreatic cancer: a retrospective, single-center observational study“(BioMed Central Palliative Care, 2019:18 (13)), all patients registered with Cabrini Health who were diagnosed with pancreatic cancer between January 2012 and December 2016, referred to the palliative care service and subsequently died, were analysed retrospectively.
In this study, early palliative care referral (PCR) was defined as referral greater than 90 days before death while late PC referral (PCR) was defined as that lesser than or equal to 90 days before death. More than one emergency department (ED) presentations, acute inpatient/intensive care unit (ICU) admission and/or chemotherapy use, were set as key indicators of aggressive cancer care in the last 30 days of life. Sixty seven percent patients had received a late PCR and 33%, an early PCR. The median time between referral and death was 48 days. Those with late PCR had 18% more Emergency Department (ED) presentations and 12.5% more acute hospital admissions while there was no difference in ICU admissions compared to early PCR group. Despite being of very limited value, approximately 20% of patients received chemotherapy in the last 30 days of life. This could have been avoided with honest conversations and early involvement of palliative care service to assist patients and families come to terms with the inevitable outcome.
Prostate cancer and breast cancer have the longest referral-to death (RTD) interval while hematological and head and neck cancers have the shortest interval. Studies demonstrate that longer RTD interval increases the likelihood of dying at home or in an inpatient hospice and the intensity of palliative care follow-up is associated with fewer instances of aggressive treatments used near death. Majority of patients who were never admitted to a palliative care unit prefer to be home at EOL, whereas those with at least one admission to a palliative care unit show preference for this setting. Dr Gaurav Kumar (Consultant Palliative care, Tata Medical Center, Kolkata) told this correspondent, “With the advent of newer targeted therapies for various cancers over the last few decades, survival of patients suffering from cancer has improved. As a manifestation of increased lifespan, symptom-burden of these patients has markedly increased and this warrants timely early referral to palliative care services. A prompt referral not only ensures good quality of life to patients and their families and patients living as comfortably as possible irrespective of the stage of cancer but also helps build a confident rapport with the palliative care team so that patients don't feel abandoned at the end of life phase, when no more cancer specific treatments are available to them”.
The study reiterates the benefits of early PCR for pancreatic cancer patients to avoid inappropriate care towards the EOL. In modern cancer care, there is a need to reconsider the use of 'aggressive cancer care' at the EOL stage when the care can be conveniently customised to an individual patient's presenting physical and psychosocial needs.
Erdafitinib: The first Targeted Therapy for Bladder Cancer
Oncology practice is progressing towards personalised approach. A major breakthrough in this process is the advent of targeted therapy which has already been in use against different molecular alterations, in leukemias, lung cancer and breast cancer. The major advantage of targeted approach is more selective killing of cells and less collateral damage. Transitional cell carcinoma, or urothelial carcinoma (UC) is the most common type of bladder cancer. Fibroblast growth factors receptors (FGFRs) are cell membrane receptors that mediate important downstream pathways regulating important biological processes, including cell growth and division during development and tissue repair. FGFR alterations are detected in approximately 20% of patients with recurrent and refractory bladder cancer.
Considering the above facts, the efficacy of Erdafitinib (Balversa) was studied in a clinical trial (study BLC2001 (NCT02365597) that included 87 patients with recurrent or refractory advanced bladder cancer with FGFR3 or FGFR2 genetic alterations, which had progressed following chemotherapy. The response rates were impressive: 30% having a partial response and 2.3% having a complete response. The median duration of response was approximately 5.5 months. On this basis, the drug received an accelerated approval by the U.S. Food and Drug Administration in April 2019, for the treatment of relapsed refractory bladder cancer patients with genetic alterations in FGFR3 or FGFR2, tested through QIAGEN's therascreen FGFR RGQ RT-PCR kit as a companion diagnostic. This approval is the first of its kind with a new novel target and new novel drug in a malignancy where no targeted therapy has been approved till date.
An accelerated approval is granted in an expeditious manner to drugs for serious diseases which qualify for an unmet medical need. Nevertheless, further clinical trials are required and are being conducted to confirm Erdafitinib's clinical benefit. The drug has side effects including increased phosphate levels, oral mucositis, fatigue, deranged kidney function, diarrhea, xerostomia, onycholysis, deranged liver functions, hyponatremia, anorexia, dysgeusia, anemia, xeroderma, xerophthalmia and alopecia. It may cause eye inflammation, necessitating periodic eye examinations. The drug is not recommended for pregnant or breastfeeding women. Regarding the clinical potential of this drug, Dr Joaquim Bellmunt (Associate Professor of Medicine, Harvard Medical School, Boston, Mass, USA) opined, “Erdafitinib, is an important milestone as we work to bring new treatment options for molecularly selected metastatic UC patients. The durable response rate seen in patients who had metastatic or surgically unresectable UC with a verified mutation in FGFR3 or fusion in FGFR2 or FGFR3 is a great achievement for our patients.”
HS Darling, New Delhi,
Potential Use of Label- free Raman Spectroscopy in Prediction of Tumor Resistance to Radiotherapy
Raman spectroscopy has been utilised in the life sciences in the detection of pigments, molecular makeup of cell structures and living tissues. Such spectroscopic images have often been able to produce a unique molecular fingerprint which differentiates it from other tissues and molecules. The spectroscopic typing of the biomolecules in past decades have been possible by using biomarkers such as dyes, tagged protein particles. The Raman spectroscopic images have high quantitative accuracy on untreated samples which are reproducible without disruption of measurement targets.
In the past decade, Raman Spectroscopy has shown promising results in life sciences without the use of histochemical markers. Raman spectroscopic imaging of tissues were done through detection of the molecular fingerprint of particles through label-free spectroscopy. Raman spectroscopy has been used in detection of collagen bands in infarcted and healthy rat- heart tissue, molecular imaging, programmed cell death by time-lapse imaging and imaging of various endocellular processes. In cancer research, the detection of the tumor resistance was possible through radiolabelled tests of cancer cells and tissues, (especially in breast and lung cancer cell lines) through multivariate analysis using Raman spectroscopy.
In a study published on April 15, 2019 (Cancer Research; 79 (8):2054-6204), titled “Label-Free Raman Spectroscopy Reveals Signatures of Radiation Resistance in the Tumor Microenvironment”,SK Paidi et al. from Johns Hopkins University, Baltimore, MD, USA, were able to demonstrate the use of label-free Raman spectroscopy for detecting the presence of tumor resistance to radiotherapy. When subjected to label-free Raman spectroscopy, radiation- resistant and sensitive human cancer cell lines for squamous cell carcinoma in lung and head and neck region in xenografts of athymic mice, showed significant differences in the tumor milieu. The in vivo specimens of untreated and treated tumor specimens, when subjected to chemometric and multivariate analysis showed significantly higher differences in lipid and collagen contents in cancer sensitive vis a vis resistant tissue. The elucidation of such changes through label-free Raman spectroscopy has shown it to be a promising tool in the early detection of tumor resistance to radiotherapy. The spectral markers in the xenografts of these athymic mice have been useful in predicting radiation responses even before the beginning of radiotherapy.
In the opinion of Dr. Vidyasagar Mamidipudi, (Consultant radiotherapist, Father Muller's Medical College, Mangalore), “The pretreatment tumor resistance assays help in the avoidance of unnecessary radiotherapy. In such cases, the addition of radiosensitizing agents would augment the response to radiation. Additionally, this technology can also be used to detect the tumor response to radiotherapy”. These advances in label-free detection through Raman Spectroscopy, could ultimately translate to formulation of a better treatment protocol by selecting suitable candidates for radiotherapy.
Ankeeta Menona Jacob, Mangalore,
ORCID - 0000-0002-9839-3556
Physics and Cancer – finding the Connection
In 2009, the National Cancer Institute, Bethesda, USA (NCI) set up the The Physical Sciences-Oncology Network (PS-ON) to use the principles and technologies from physics to study the physical dynamics of cancer and to understand the spatio-temporal organisation and transfer of information in cancer. The aim was to use mathematics and physics to study the role of physical factors and microenvironment factors in cancer to complement the Cancer Systems Biology Consortiums of NCI and further aid the cancer therapies.
A decade into the research in the field, the findings of this research were published by Forest M White et al. in “The Physics of Cancer” (Cancer Research 2019;79 (9):2107-10) on 1st May 2019. The major findings of this research were:
Physical properties of cancer cells and their micro-environment: Besides genetics and tumor suppressing and promoting factors, abnormalities in physical environment play an important role in tumorigenesis. Though it had been known for long that tumors have aberrations in transport mechanism, which are responsible for differences in metabolism compared to normal cells, the fact that tissue mechanics and abnormal transport mechanisms can be independent risk factors for malignant transformation has only been recently demonstrated in this study. As a result of host response to cancer cells and in attempts to create a niche to enhance their fitness at the expense of normal cells, cancer cells form a micro-environment comprising diverse 3D tissue and extracellular matrix architecture and matrix, changes in physical properties of single cells, gradient of soluble factors, interstitial pressure and transport process. This physical micro-environment has a complex interplay with the factors of mechanical deformity, cytoplasmic viscoelasticity, cellular traction forces and response to pH and stress (which are significantly different between less and more aggressive tumors) to determine the aggressiveness and invasiveness of tumors. The study also revealed that tumor cell physical properties keep changing with a change in their functions. The ability of the tumor cells to migrate depends on the capacity of the cells to modify their nuclear mechanisms to go past any constrictions. The alterations in intracellular forces can change the DNA of the tumor cells. This association could potentially be used for cancer therapyUtilisation of physical sciences to measure cancers at small and large dimensions: Cancer cells undergo resistant mutations which is determined by the number of pre-existing cells with these mutations. Due to the extraordinary ability of cancer cells to evolve mechanisms to bypass therapy, common disseminated cancers remain fatal without exception. This PS-ON study has developed mechanism to quantify in real time the number of circulating tumor cells (CTC) while the patient is on chemotherapy to measure the response to therapy. Cell mass, molecular characterisation and proliferation rates are quantified by single cell sequencing of RNAs of 100s to 1000s of CTCs from tumors. In solid tumors, the micro-environment dictates the physical and molecular pattern, which is not adequately summarised by CTCs. Magnetic resonance imaging, SRS (simulated Raman scattering), matrix assisted mass spectrograph are being utilized to study the response of solid tumors to therapy.
The aim of this study was to bridge the gap between physical and biological sciences to discover the dynamics and evolution of cancer and to improve the responses of current therapy for cancer. The study observed that though the terminology of “precision medicine” characterises tumors on the basis of molecular data; temporal and spatial variations in tumor micro-environment play an important role in tumor spread and have to be taken into consideration to develop more effective treatments for cancer. The limitation of the study was the need for better in vitro models which can be used to discover and target the molecular mechanisms that are influenced by the physical forces in the tumor micro-environment. More research is needed to substantiate this association.
Neha Chauhan, Bangalore