Surgery is the standard of care for patients with primary renal cell carcinoma. Stereotactic body radiotherapy (SBRT) is a novel alternative for patients who are medically inoperable, technically high risk, or who decline surgery. Evidence for using SBRT in the primary renal cell carcinoma setting is growing, including several rigorously conducted prospective clinical trials. This systematic review was performed to assess the safety and efficacy of SBRT for primary renal cell carcinoma. Review results then formed the basis for the practice guidelines described, on behalf of the International Stereotactic Radiosurgery Society. 3972 publications were screened and 36 studies (822 patients) were included in the analysis. Median local control rate was 94·1% (range 70·0–100), 5-year progression-free survival was 80·5% (95% CI 72–92), and 5-year overall survival was 77·2% (95% CI 65–89). These practice guidelines addressed four key clinical questions. First, the optimal dose fractionation was 25–26 Gy in one fraction, or 42–48 Gy in three fractions for larger tumours. Second, routine post-treatment biopsy is not recommended as it is not predictive of patient outcome. Third, SBRT for primary renal cell carcinoma in a solitary kidney is safe and effective. Finally, guidelines for post-treatment follow-up are described, which include cross-axial imaging of the abdomen including both kidneys, adrenals, and surveillance of the chest initially every 6 months. This systematic review and practice guideline support the practice of SBRT for primary renal cell carcinoma as a safe and effective standard treatment option. Randomised trials with surgery and invasive ablative therapies are needed to further define best practice.
Squamous-cell carcinoma
Five-MicroRNA Signature: Predicting Outcomes in HPV-Negative Head and Neck Cancer
The prognosis for human papillomavirus (HPV)-negative head and neck squamous cell carcinoma is generally poorer than for those with HPV-positive disease. Dr. Julia Hess, of the German Research Center for Environmental Health GmbH in Neuherberg, and colleagues sought to find prognostic markers to help predict the risk of recurrence in this patient population and thus create personalized treatments with radiation, targeted drugs, and immune checkpoint inhibitors. They may have succeeded: By retrospectively performing microRNA (miRNA) expression profiling, they discovered a “five-miRNA signature [that] is a strong and independent prognostic factor for disease recurrence and survival of patients with HPV-negative head and neck squamous cell carcinoma,” the authors reported. Of note, added Dr. Hess in Clinical Cancer Research, “its prognostic significance is independent from known clinical parameters.”
The five-miRNA signature, when combined with established risk factors, allowed four prognostically distinct groups to be defined. Recursive-partitioning analysis classified 162 patients into being at low (n = 17), low-intermediate (n = 80), high-intermediate (n = 48), or high risk (n = 17) for recurrence (P < .001).
“[The five-miRNA signature] represents the basis for a more focused search for molecular therapeutic targets,” which would potentially improve “therapy success for appropriate patients,” the researchers stated. Currently, even when given state-of-the-art, standard-of-care therapy, patients with HPV-negative head and neck squamous cell carcinoma cancer have an overall survival rate of only about 50%.
Are Current Staging Systems for Cutaneous Squamous Cell Carcinoma Satisfactory?
According to the results of a nested case-control study, “four current staging systems distinguished poorly to moderately between [cutaneous squamous cell carcinoma] patients who developed metastasis and those who did not.” The worst-performing system was that of American Joint Committee on Cancer (AJCC), 7th edition, in its “ability to cluster patients with similar outcomes within the same staging category,” wrote the researchers in JAMA Dermatology.
Ingrid Roscher, MD, of Oslo University Hospital, and colleagues also evaluated systems used by Breuninger et al and Boston’s Brigham and Women’s Hospital (Brigham), as well as the AJCC, 8th edition. They identified all patients in Norway diagnosed with primary invasive cutaneous squamous cell carcinoma between 2000 and 2004 (n = 6,721) and then the 112 patients diagnosed with metastasis within 5 years. These patients were randomly paired with 112 controls, matched for sex and age, whose cutaneous squamous cell carcinoma had not metastasized. Expert histologic reexamination of the biopsies yielded 103 patients with metastasis and 81 without.
Results indicated that in the systems used by Breuninger et al and Brigham, high-risk categories for diameter and tumor thickness (Breuninger) and the T2b category (Brigham) collected relatively homogeneous groups. And in both those systems, “risk of metastasis was significantly elevated with increasing stage or risk category.” External validation was performed by logistic regression, discrimination, and calibration statistics. The team found that all four staging systems were lacking in the ability to predict who would and who would not develop metastases.
“A staging system for [cutaneous squamous cell carcinoma] has to be suitable for use in everyday clinical practice,” revealed Dr. Roscher and colleagues. “Variables included in the four staging systems validated in this study may be difficult to assess accurately, which give them limited value for clinicians.”
In clinical trial, cream reduces squamous cell carcinoma risk
Common Blood Pressure Drug Tied to Increased Risk of Skin Cancer
People who take a certain diuretic prescribed to control fluid retention and treat high blood pressure may be more likely to get skin cancer than other individuals, a Danish study suggests.
While the drug, hydrochlorothiazide, has long been linked to an increased risk of sunburns, the current study offers fresh evidence that this commonly prescribed medication may also make people more likely to develop basal cell carcinoma and squamous cell carcinoma.
For the study, researchers examined national prescription registry data on hydrochlorothiazide use from 1995 to 2012 as well as cancer registry records on skin malignancies diagnosed from 2004 to 2012.
Overall, people who took hydrochlorothiazide daily for at least six years were 29% more likely to develop basal cell carcinoma and almost four times more likely to get squamous cell carcinoma than individuals who didn’t take this medication, the study found.
“We already knew that hydrochlorothiazide makes the skin more vulnerable to damage from UV light of sun or sunbeds,” said senior study author Anton Pottegard of the University of Southern Denmark.
“However, we did not know that hydrochlorothiazide use also appears to translate into an increased risk of non-melanoma skin cancer,” Pottegard said by email.
The study included more than 71,000 people with basal cell carcinoma, 8,600 patients with squamous cell carcinoma, and a control group of more than 313,000 people in the Danish population who didn’t have these malignancies but were otherwise similar to the cancer patients.
About 2.7% of patients with basal cell carcinoma and 2.1% of the control group were high users of hydrochlorothiazide, with a lifetime cumulative dose of at least 50,000 mg, or roughly six years of daily use.
Ten percent of squamous cell carcinoma cases were high users, as were 2.8% of people in the control group.
With the highest cumulative hydrochlorothiazide exposure – approximately 24 years of daily use – patients were 54% more likely to develop basal cell carcinoma and more than seven times more likely to get squamous cell carcinoma.
The study wasn’t a controlled experiment designed to prove whether or how hydrochlorothiazide might cause skin cancer.
Another limitation is that researchers lacked data on two main factors that influence the risk of skin cancer: ultraviolet light exposure and skin type, the study authors note online December 3 in the Journal of the American Academy of Dermatology.
“There may be a relationship between taking hydrochlorothiazide and risk for skin cancer,” said Dr. Aaron Farberg of the Icahn School of Medicine at Mount Sinai in New York City.
“However, the relationship may not be directly causative,” Farberg, who wasn’t involved in the study, said by email.
Even so, the findings add to the evidence suggesting that patients taking hydrochlorothiazide should take extra precautions to protect their skin from damage caused by the sun, said Dr. Elizabeth Martin, president of Pure Dermatology & Aesthetics in Hoover, Alabama.
“Everyone can reduce their skin cancer risk by avoiding unprotected exposure to UV light,” Martin, who wasn’t involved in the study, said by email. “Don’t use indoor tanning devices, and protect yourself from the sun by seeking sunscreen with an SPF of 30 or higher.”
Patients taking hydrochlorothiazide shouldn’t stop without first seeing a doctor, Pottegard cautioned. While there are other safe, affordable options to manage high blood pressure, patients already taking hydrochlorothiazide won’t meaningfully alter their skin cancer risk by staying on the drug for a few months until a physician can advise them, he said.
“If you are at an increased risk of skin cancer, due to high exposure to sunlight, have already experienced skin cancer, or are otherwise predisposed to skin cancer, you should consider consulting your physician regarding a potential therapy shift,” Pottegard said.
Early Detection of Recurrent Disease by FDG-PET/CT Leads to Management Changes in Patients With Squamous Cell Cancer of the Head and Neck.
Abstract
Objective. The objective of this study was to compare the efficacy of surveillance high-resolution computed tomography (HRCT) and physical examination/endoscopy (PE/E) with the efficacy of fluorodeoxyglucose (FDG)-positron emission tomography (PET)/HRCT for the detection of relapse in head and neck squamous cell carcinoma (HNSCC) after primary treatment.
Methods. This is a retrospective analysis of contemporaneously performed FDG-PET/HRCT, neck HRCT, and PE/E in 99 curatively treated patients with HNSCC during post-therapy surveillance to compare performance test characteristics in the detection of early recurrence or second primary cancer.
Results. Relapse occurred in 19 of 99 patients (20%) during a median follow-up of 21 months (range: 9–52 months). Median time to first PET/HRCT was 3.5 months. The median time to radiological recurrence was 6 months (range: 2.3–32 months). FDG-PET/HRCT detected more disease recurrences or second primary cancers and did so earlier than HRCT or PE/E. The sensitivity, specificity, and positive and negative predictive values for detecting locoregional and distant recurrence or second primary cancer were 100%, 87.3%, 56.5%, and 100%, respectively, for PET/HRCT versus 61.5%, 94.9%, 66.7%, and 93.8%, respectively, for HRCT versus 23.1%, 98.7%, 75%, and 88.6%, respectively, for PE/E. In 19 patients with true positive PET/HRCT findings, a significant change in the management of disease occurred, prompting either salvage or systemic therapy. Of the 14 curatively treated patients, 11 were alive with without disease at a median follow-up of 31.5 months.
Conclusion. FDG-PET/HRCT has a high sensitivity in the early detection of relapse or second primary cancer in patients with HNSCC, with significant management implications. Given improvements in therapy and changes in HNSCC biology, appropriate modifications in current post-therapy surveillance may be required to determine effective salvage or definitive therapies.
Source: The Oncologist.
Specific Oncogene Plays a Role in Lung Squamous Cell Carcinoma.
The identification of an oncogene (called BRF2) specific to lung squamous cellcarcinoma suggests that genetic activation of this oncogene could be used as an identification marker for this type of lung cancer. Furthermore, this oncogene may provide a new target for therapeutics for lung squamous cell carcinoma.
These findings come from a study by William Lockwood and colleagues from the BC Cancer Agency‘s Research Centre in Vancouver, Canada, and are reported in PLoS Medicine.
Lung cancer is the most common cause of cancer-related death, killing 1.3 million people every year worldwide. Most cases of lung cancer are “non-small cell lung cancers” of which there are 2 main types: squamous cell carcinoma and adenocarcinoma.
The authors used a comparative genetic hybridisation technique to show that the focal amplification of chromosome region 8p12 plays a role in the development of lung squamous cell carcinoma (in about 40% of cases) but not in the development of lung adenocarcinoma where DNA loss in this chromosomal region is the most common alteration. The oncogene BRF2 was frequently activated in pre-invasive stages of lung squamous cell carcinoma — carcinoma in situ and dysplasia.
The authors conclude: “This is the first study, to our knowledge, to show that the focal amplification of a gene in chromosome 8p12 plays a key role in squamous cell lineage specificity of the disease. Our data suggest that genetic activation of BRF2 represents a unique mechanism of lung squamous cell carcinoma tumorgenesis.” They add, “It [BRF2] can serve as a marker of lung squamous cell carcinoma and may provide a novel target for therapy.”
Source: http://www.sciencedaily.com
Indoor tanning and non-melanoma skin cancer: systematic review and meta-analysis.
Abstract
Objective To synthesise the literature on indoor tanning and non-melanoma skin cancer.
Design Systematic review and meta-analysis.
Data sources PubMed (1966 to present), Embase (1974 to present), and Web of Science (1898 to present).
Study selection All articles that reported an original effect statistic for indoor tanning and non-melanoma skin cancer were included. Articles that presented no data, such as review articles and editorials, were excluded, as were articles in languages other than English.
Data extraction Two investigators independently extracted data. Random effects meta-analysis was used to summarise the relative risk of ever use versus never use of indoor tanning. Dose-response effects and exposure to indoor tanning during early life were also examined. The population attributable risk fraction for the United States population was calculated.
Results 12 studies with 9328 cases of non-melanoma skin cancer were included. Among people who reported ever using indoor tanning compared with those who never used indoor tanning, the summary relative risk for squamous cell carcinoma was 1.67 (95% confidence interval 1.29 to 2.17) and that for basal cell carcinoma was 1.29 (1.08 to 1.53). No significant heterogeneity existed between studies. The population attributable risk fraction for the United States was estimated to be 8.2% for squamous cell carcinoma and 3.7% for basal cell carcinoma. This corresponds to more than 170 000 cases of non-melanoma skin cancer each year attributable to indoor tanning. On the basis of data from three studies, use of indoor tanning before age 25 was more strongly associated with both squamous cell carcinoma (relative risk 2.02, 0.70 to 5.86) and basal cell carcinoma (1.40, 1.29 to 1.52).
Conclusions Indoor tanning is associated with a significantly increased risk of both basal and squamous cell skin cancer. The risk is higher with use in early life (<25 years). This modifiable risk factor may account for hundreds of thousands of cases of non-melanoma skin cancer each year in the United States alone and many more worldwide. These findings contribute to the growing body of evidence on the harms of indoor tanning and support public health campaigns and regulation to reduce exposure to this carcinogen.
Source: BMJ
ARYAN'S BLOG 