Metabolic response to radiation therapy in cancer.

Tumor metabolism has emerged as a hallmark of cancer and is involved in carcinogenesis and tumor growth. Reprogramming of tumor metabolism is necessary for cancer cells to sustain high proliferation rates and enhanced demands for nutrients. Recent studies suggest that metabolic plasticity in cancer cells can decrease the efficacy of anticancer therapies by enhancing antioxidant defenses and DNA repair mechanisms. Studying radiation-induced metabolic changes will lead to a better understanding of radiation response mechanisms as well as the identification of new therapeutic targets, but there are few robust studies characterizing the metabolic changes induced by radiation therapy in cancer. In this review, we will highlight studies that provide information on the metabolic changes induced by radiation and oxidative stress in cancer cells and the associated underlying mechanisms.

Viral Burden and Clearance in Asymptomatic COVID-19 Patients.

Background: Containing coronavirus disease 2019 (COVID-19) has been difficult, due to both the large number of asymptomatic infected individuals and the long duration of infection. Managing these challenges requires understanding of the differences between asymptomatic vs symptomatic patients and those with a longer duration of infectivity. Methods: Individuals from Los Angeles were tested for COVID-19, and a group positive for COVID-19 chose to have follow-up testing. Associations between symptoms and demographic factors, viral burden measured by cycle threshold (CT) value, and duration of polymerase chain reaction (PCR) positivity were analyzed. Results: Eighteen point eight percent of patients were positive for COVID-19. Asymptomatic COVID-19-positive patients were significantly younger than symptomatic patients (2.6 years; P < .001). There were no differences in average CT between asymptomatic and symptomatic patients. The estimated median duration of COVID-19 PCR positivity was 23 days. Being asymptomatic throughout the course of infection was the only factor associated with a shorter course of COVID-19 PCR positivity (21 vs 28 days; P = .002). Conclusions: We found important differences and similarities between asymptomatic and symptomatic COVID-19-positive patients, the most meaningful being a similar level of virus as measured by PCR, but a shorter duration of PCR positivity for asymptomatic patients. These findings suggest that asymptomatic patients may have more efficient clearance of virus, which may be relevant for management and screening.

Breast Cancer and miR-SNPs: The Importance of miR Germ-Line Genetics.

Recent studies in cancer diagnostics have identified microRNAs (miRNAs) as promising cancer biomarkers. Single nucleotide polymorphisms (SNPs) in miRNA binding sites, seed regions, and coding sequences can help predict breast cancer risk, aggressiveness, response to stimuli, and prognosis. This review also documents significant known miR-SNPs in miRNA biogenesis genes and their effects on gene regulation in breast cancer, taking into account the genetic background and ethnicity of the sampled populations. When applicable, miR-SNPs are evaluated in the context of other patient factors, including mutations, hormonal status, and demographics. Given the power of miR-SNPs to predict patient cancer risk, prognosis, and outcomes, further study of miR-SNPs is warranted to improve efforts towards personalized medicine.

Three-dimensional alginate hydrogels for radiobiological and metabolic studies of cancer cells.

The purpose of this study is to demonstrate calcium alginate hydrogels as a system for in vitro radiobiological and metabolic studies of cancer cells. Previous studies have established calcium alginate as a versatile three-dimensional (3D) culturing system capable of generating areas of oxygen heterogeneity and modeling metabolic changes in vitro. Here, through dosimetry, clonogenic and viability assays, and pimonidazole staining, we demonstrate that alginate can model radiobiological responses that monolayer cultures do not simulate. Notably, alginate hydrogels with radii greater than 500 µm demonstrate hypoxic cores, while smaller hydrogels do not. The size of this hypoxic region correlates with hydrogel size and improved cell survival following radiation therapy. Hydrogels can also be utilized in hyperpolarized magnetic resonance spectroscopy and extracellular flux analysis. Alginate therefore offers a reproducible, consistent, and low-cost means for 3D culture of cancer cells for radiobiological studies that simulates important in vivo parameters such as regional hypoxia and enables long-term culturing and in vitro metabolic studies.

Short course para-aortic radiation for stage I seminoma of the testis.

PURPOSE: To determine the outcome in men with Stage I seminoma treated with low-dose para-aortic radiation. MATERIALS AND METHODS: Between January 1988 and December 2000, 431 men with Stage I seminoma were treated with para-aortic radiation to a midplane dose of 20 Gy in 8 fractions over 10 days. RESULTS: At a median follow-up of 62 months, 15 patients (3.5%) had relapsed, with a median time to relapse of 13 months (range: 9 to 39 months). Nine patients had pelvic nodal relapse; in addition, 1 patient had para-aortic involvement, and 2 had distant disease. Four had metastatic disease only (mediastinum 2, lung 2). One patient had scrotal recurrence, and 1 was treated for progressive rise in human chorionic gonadotrophin without identifiable disease. Initial treatment at relapse was chemotherapy (12), radiation (2), and surgery (1). One patient died from progressive disease. Thirteen men (3%) have developed second malignancies, including 7 contralateral testicular tumors, 5 solid malignancies, and 1 leukemia. The overall 5-year survival was 98%, and the estimated recurrence-free survival at 5 years was 96.3%. On log-rank univariate analysis, lymphovascular invasion, involvement of the tunica, and a preoperative human chorionic gonadotrophin level of greater than 5 were found to be of prognostic significance for recurrence. CONCLUSIONS: These data support short-duration, limited-field radiation as an optimal safe and effective protocol in the management of Stage I seminoma patients.

Hypofractionated conformal radiotherapy in carcinoma of the prostate: five-year outcome analysis.

PURPOSE: Recent publications have indicated that the alpha/beta ratios for carcinoma of the prostate are much lower than had originally been thought, suggesting that prostate cancer may be highly sensitive to fraction size. We have reviewed our unique experience of the use of 3.13 Gy fractions in a large cohort of men treated homogeneously in a single institute. MATERIALS AND METHODS: The outcome for 705 men with T1-T4, N0, M0 prostate cancer who received conformal radiotherapy between 1995 and 1998 at this center was analyzed. No patient received hormonal manipulation. Mean age was 68 years (range: 49-84 years). Median pretreatment PSA was 13 ng/mL (range: 0.6-270 ng/mL). Disease characteristics were as follows: Stage T1, 125 (18%); T2, 365 (52%); T3/4, 215 (30%); Gleason 2-6, 463 (66%); Gleason 7-10, 242 (34%); pretreatment PSA < or =10 ng/mL, 291 (41%); 10 to < or =20, 228 (32%); >20, 186 (27%). Median follow-up was 48 months (range: 1-82 months). Biochemical-free survival (bNED) was defined by the American Society for Therapeutic Radiology and Oncology consensus definition. Radiotherapy was delivered to a planning target volume (prostate plus all/base of the seminal vesicles dependent on risk criteria with a 1-cm margin) with a 4-field conformal technique to a dose of 50 Gy in 16 daily fractions over 22 days. RESULTS: The 5-year bNED survival was significantly associated (p < 0.001) with pretreatment PSA, stage, and Gleason score. Five-year bNED rates with respect to pretreatment characteristics were as follows: 73% (PSA < or =10), 52% (>10-20), 35% (>20), 64% (Stage T1/2), 38% (T3/4), 61% (Gleason score 2-6), and 46% (Gleason > or =7). When patients were grouped into good (Stage T1/2, PSA < or =10 ng/mL, and Gleason score <7) (n = 181), intermediate (1 raised value) (n = 247), or poor (2 or more raised values) (n = 277) prognostic groups, the bNED was, respectively, 82%, 56%, and 39%. Radiation Therapy Oncology Group Grade > or =2 bowel toxicity was 5% and bladder 9%. CONCLUSIONS: These data indicate that the delivery of a relatively low total dose using a hypofractionated regime results in similar tumor control and normal-tissue toxicity to 65-70 Gy delivered in 1.8-2 Gy fractions. These data suggest that this is an acceptable regime for good-prognosis patients. However, because of the evidence for a dose effect at doses above 70 Gy with "conventional fractionation," we are now treating intermediate- and poor-risk patients within a hypofractionated dose escalation trial to 60 Gy in 20 fractions using intensity- modulated radiotherapy.

Radiotherapy for muscle-invasive carcinoma of the bladder: results of a randomized trial comparing conventional whole bladder with dose-escalated partial bladder radiotherapy.

PURPOSE: To investigate whether delivering an increased radiation dose to the tumor-bearing region of the bladder alone would improve local disease control without increasing treatment toxicity. METHODS AND MATERIALS: A total of 149 patients with unifocal T2-T3N0M0 bladder carcinoma were randomized between whole bladder conformal radiotherapy (WBRT, 52.5 Gy in 20 fractions, n = 60) and partial bladder conformal RT (PBRT) to tumor alone with 1.5-cm margins within either 4 weeks (PBRT4, 57.5 Gy in 20 fractions, n = 44) or 3 weeks (PBRT3, 55 Gy in 16 fractions, n = 45). The response was assessed cystoscopically after 4 months. RESULTS: The 5-year overall and CFS rate was 58% and 47%, respectively, for the whole population. The CR rate was 75% for WBRT, 80% for PBRT4, and 71% for PBRT3 (p = 0.6), with a 5-year local control rate of 58%, 59%, and 34%, respectively (p = 0.18). Solitary new tumors arose within the bladder, outside the irradiated volume, in 6 (7%) of 89 patients who underwent PBRT. The 5-year overall survival and cystectomy-free survival rate was 61% and 49% for WBRT, 60% and 50% for PBRT4, and 51% and 41% for PBRT3 (p = 0.81 and p = 0.59). The treatment toxicity was mild and equivalent across the three trial arms. CONCLUSION: The reduction in treatment volume allowed delivery of an increased radiation dose without a reduction in local tumor control or the development of excess toxicity. However, this dose-escalated partial bladder approach did not result in significantly improved overall survival.

A subjective study of dimensional stability of permanent acrylic resin complete denture bases after a second curing cycle.

The aim of this study was to subjectively assess permanent denture base retention and stability in order to determine whether detrimental change occurred as a result of a second curing cycle. 100 complete upper denture bases were assessed by clinician and patient using visual analogue scales at try-in and insert. No statistically significant alteration in mean scores for retention and stability was seen. 5% of bases showed some deterioration, but none required rebasing or remaking as a result. The advantages of permanent bases during denture construction seem to outweigh the risk of loss of retention and/or stability as a result of distortion due to the second curing cycle.

Socio-economic inequalities in testicular cancer survival within two clinical studies.

BACKGROUND: Testicular cancer is the most common cancer in men under 35 years of age, and has the highest survival for adult male malignancies. Despite the fact that survival is very high, there is evidence that survival differs between socio-economic groups. METHODS: We analysed survival patterns for 1606 testicular cancer patients diagnosed during 1984-2001 and recruited to one of two clinical studies. The first was a surveillance study to determine relapse-free survival after orchidectomy in 865 patients with stage I nonseminomatous germ-cell testicular cancer diagnosed during 1984-1991 (TE04). The second study was a trial in which 1174 men with stage I seminomatous germ-cell tumours were randomised to receive radiotherapy or one injection of carboplatin between 1996 and 2001 (TE19). The number of men available for analysis from these two studies was 578 and 1028, respectively. We followed these patients up for their vital status, and assigned them an ecological measure of deprivation. Crude and relative survival were estimated at 5 and 10 years by socio-economic deprivation. RESULTS: No significant socio-economic gradient was seen: 1.3% (95% CI -0.3% to 3.1%) at 5 years and 2.1% (95% CI -0.5% to 4.7%) at 10 years. CONCLUSION: We conclude that, given equal treatment at a given stage of disease, survival from testicular cancer does not depend on socio-economic status. This suggests that the socio-economic gradient in testicular cancer survival in the general population is more likely to be attributable to health care system factors than to personal or socio-economic factors in the men themselves.