Breast Cancer Adjuvant Radiotherapy in Up-Front to Chemotherapy: Is There a Worthwhile Benefit? A Preliminary Report.

Purpose: We administered a new breast cancer (BC) adjuvant therapy sequence that delivered postoperative radiotherapy (PORT) before chemotherapy (CT). Our aim was to assess the gain in time to start PORT and the G2-G3 acute-subacute toxicity rate of whole breast adjuvant hypofractionated radiotherapy (AH-RT) administered up-front to the third-generation adjuvant CT (A-CT) in high-risk nodal positive BC in a preliminary report at 2 years. Methods: This retrospective study analysed the duration of treatment and safety of AH-RT administered up-front to A-CT in high-risk nodal positive BC patients (pts). Data on 45 pts treated between 2022-2023 were collected. All pts underwent the third-generation A-CT after AH-RT 15-5 fractions with or without a boost. Acute toxicity was scored according to CTCAE v5.0 for skin, pulmonary, and cardiac adverse events. Univariate and multivariate analyses were conducted to assess significant prognosticators for skin/lung/heart acute toxicities in the AH-RT 5-15 fractions arms and CT (p < 0.005). Results: A reduction in the time to PORT initiation and overall adjuvant treatment time was recorded. RT was initiated 5 median weeks after surgery, and A-CT was performed 9 median weeks after surgery. The median duration of the entire adjuvant treatment was 35 weeks after surgery. At 6 months mean follow-up, no significant differences in G2-G3 toxicity were noted between the different hypofractionated RT arms, irrespective of the CT schedules, irradiated volumes, or boost (SIB or sequential) in univariate and multivariate analyses. In the multivariate analysis, no significant effects in CT schedules and AH-RT 5-15 arms for skin/lung acute toxicities (p = 0.077 and p = 0.68; 0.67 and 0.87, respectively) were recorded. Conclusion: As a new PORT approach in BC, AH-RT up-front to the third-generation A-CT appeared safe with a low acute toxicity profile, providing an advantage in shortening the time from surgery to PORT initiation and the overall adjuvant treatment time.

Radiation Recall Pneumonitis COVID-19 Infection Induced After Adjuvant Breast Cancer Radiotherapy. A Known Phenomenon in an Unknown Pandemic Disease: A Case Report.

The COVID-19 pandemic has opened several new disease scenarios, yielding novel syndromes that have never been seen before and resurrecting old inflammatory phenomena that are no longer recorded, such as radiation recall (RR) syndromes. Radiation recall syndrome is a limited field inflammatory reaction that occurs in a volume that was irradiated several months or years previously before being induced by a triggering factor. The most frequently reported phenomena are skin reactions; however, other organs could be involved, such as the lungs in radiation recall pneumonitis (RRP). It is a well-described inflammatory reaction that occurs within a pulmonary volume that was irradiated several months or years previously via radiotherapy (RT), triggered by factors such as drugs, including chemotherapy agents, immunotherapy, or vaccination. Indeed, during the COVID-19 pandemic, RRP following anti-COVID-19 vaccination or SARS-CoV2 infection was recently reported. ACE receptor-rich tissues such as lung or skin tissues were mainly involved. Herein, we present a case of RRP triggered by COVID-19 pulmonary infection in a woman who previously underwent adjuvant breast cancer radiotherapy. Although symptoms were typical, pulmonary CT findings depicted a unique distribution of ground-glass opacities (GGOs) throughout the previous radiation portals and mirror-like the radiation fields. Anamnesis and radiation plan evaluation were crucial in the diagnosis of RRP.

Modulation of Peripheral Immune Cell Subpopulations After RapidArc/Moderate Hypofractionated Radiotherapy for Localized Prostate Cancer: Findings and Comparison With 3D Conformal/Conventional Fractionation Treatment.

Radiotherapy (RT) is an important therapeutic option in patients with localized prostate cancer (PC). Unfortunately, radiation treatment causes a decrease in peripheral lymphocytes and, consequently, influences the patients' immune status. Our aim was to study changes in peripheral blood immune cell subpopulations after RT and during 6 months' follow-up in 2 groups of PC patients irradiated with different techniques and dose fractions with curative intent. We also investigated the presence of correlation between immune cell modulation and genitourinary or gastrointestinal toxicity. We enrolled 44 patients treated with curative RT (RapidArc/hypofractionation regimen or 3D conformal/conventional fractionation) for localized PC. Total white blood cell (WBC), absolute lymphocyte counts (ALCs), and peripheral immune cell subpopulations were analyzed at baseline, at the end of RT, and 3 and 6 months after the end of RT. WBC and ALC greatly decreased at the end of RT with a trend to recover at 6 months' follow-up in the hypofractionation group but not in the conventional one. Furthermore, B, total T, T CD4+, T CD8+, and NK cell values dropped significantly in both groups at the end of RT, with a minor decrease detectable in the hypofractionation group for B, total T, and T CD4+ lymphocytes with respect to the other technique/fractionation group. Double-negative T (DNT), double-positive T (DPT), and NKT cells significantly decreased at the end of RT with a slight tendency to recover values during follow-up, particularly in the hypofractionation group. No correlation with genitourinary or gastrointestinal toxicity was found. In this study, we showed, for the first time, the effects of RapidArc/moderate hypofractionation RT on immune cell subsets in patients treated for localized PC. Due to the growing interest in minority T-cell subpopulations for immunotherapy, we also reported longitudinal monitoring of the effects of RT on DNT, DPT, and NKT, which was never studied before. Our preliminary data highlight the importance of considering the effects of different RT techniques/fractionation regimens on peripheral immune cells, in the era of RT and immunotherapy combination.

Temperature Effects During a Sublethal Chronic Metal Mixture Exposure on Common Carp (Cyprinus carpio).

The aquatic environment is the final sink of various pollutants including metals, which can pose a threat for aquatic organisms. Waterborne metal mixture toxicity might be influenced by environmental parameters such as the temperature. In the present study, common carp were exposed for 27 days to a ternary metal mixture of Cu, Zn, and Cd at two different temperatures, 10 and 20°C. The exposure concentrations represent 10% of the 96 h-LC50 (concentration lethal for the 50% of the population in 96 h) for each metal (nominal metal concentrations of Cu: 0.08 µM; Cd: 0.02 µM and Zn: 3 µM). Metal bioaccumulation and toxicity as well as changes in the gene expression of enzymes responsible for ionoregulation and induction of defensive responses were investigated. Furthermore the hepatosomatic index and condition factor were measured as crude indication of overall health and energy reserves. The obtained results showed a rapid Cu and Cd increase in the gills at both temperatures. Cadmium accumulation was higher at 20°C compared to 10°C, whereas Cu and Zn accumulation was not, suggesting that at 20°C, fish had more efficient depuration processes for Cu and Zn. Electrolyte (Ca, Mg, Na, and K) levels were analyzed in different tissues (gills, liver, brain, muscle) and in the remaining carcasses. However, no major electrolyte losses were observed. The toxic effect of the trace metal ion mixture on major ion uptake mechanisms may have been compensated by ion uptake from the food. Finally, the metal exposure triggered the upregulation of the metallothionein gene in the gills as defensive response for the organism. These results, show the ability of common carp to cope with these metal levels, at least under the condition used in this experiment.

Effect of Groundwater Age and Recharge Source on Nitrate Concentrations in Domestic Wells in the San Joaquin Valley.

Nitrate is one of the most abundant contaminants in groundwater globally, in the United States, and in California (CA). We studied well construction information, water chemistry, stable isotopes, and noble gases to understand how groundwater travel time and recharge source and mechanism control nitrate concentrations in domestic wells in the San Joaquin Valley (SJV), CA, a large semiarid, irrigated agricultural region. Using nonparametric statistics, we find a decreasing trend in nitrates with groundwater travel time and well depth. Samples collected from wells that are closer to rivers and that show indications of river water recharge, either low recharge temperature or low δ18O signature, have lower concentrations of nitrates than samples with isotopic signatures indicating mixed source or local precipitation recharge. The curbing effect of river water recharge on nitrate concentrations in domestic wells is similar for direct river recharge and water applied as irrigation. This suggests that irrigation with river water also has a diluting effect that reduces the concentration of nitrate found in groundwater. This conclusion supports the idea that flood-managed aquifer recharge may be considered for remediation of groundwater nitrate when designing replenishment of aquifers.

A comparative study on the effects of three different metals (Cu, Zn and Cd) at similar toxicity levels in common carp, Cyprinus carpio.

To improve our understanding of underlying toxic mechanisms, it is important to evaluate differences in effects that a variety of metals exert at concentrations representing the same toxic level to the organism. Therefore, the main goal of the present study was to compare the effects of waterborne copper (Cu(II)), zinc (Zn(II)) and cadmium (Cd (II)) on a freshwater fish, the common carp (Cyprinus carpio), at concentrations being 0%, 25%, 50% and 100% of the 96 h LC50 (the concentration which is lethal to 50% of the population in 96 h). All the exposures were performed for a period of 1 week at 20°C. Our results show a rapid increase in the amount of copper and cadmium accumulated in the gills, while zinc only started to increase by the end of the experiment. All three metal ions increased metallothionein gene expression in both gills and liver. However, clear adverse effects were mainly observed for the Cu exposed group. Cu caused a decrease in Na level in gill tissue; it altered the expression of genes involved in ionoregulation such as Na+ /K+ -ATPase and H+ -ATPase as well as the expression of oxidative stress-related genes, such as catalase, glutathione reductase and glutathione S-transferase. Zinc and cadmium exposure did not alter the ion levels in the gills. In addition, no obvious effect of oxidative stress was observed, except for a transient increase in glutathione reductase at the highest cadmium concentration.

Environmental plasticity and colonisation history in the Atlantic salmon microbiome: A translocation experiment.

Microbial communities associated with the gut and the skin are strongly influenced by environmental factors, and can rapidly adapt to change. Historical processes may also affect the microbiome. In particular, variation in microbial colonisation in early life has the potential to induce lasting effects on microbial assemblages. However, little is known about the relative extent of microbiome plasticity or the importance of historical colonisation effects following environmental change, especially for nonmammalian species. To investigate this we performed a reciprocal translocation of Atlantic salmon between artificial and semi-natural conditions. Wild and hatchery-reared fry were transferred to three common garden experimental environments for 6 weeks: standard hatchery conditions, hatchery conditions with an enriched diet, and simulated wild conditions. We characterized the faecal and skin microbiome of individual fish before and after the environmental translocation, using a BACI (before-after-control-impact) design. We found evidence of extensive microbiome plasticity for both the gut and skin, with the greatest changes in alpha and beta diversity associated with the largest changes in environment and diet. Microbiome richness and diversity were entirely determined by environment, with no detectable effects of fish origin, and there was also a near-complete turnover in microbiome structure. However, we also identified, for the first time in fish, evidence of historical colonisation effects reflecting early-life experience, including ASVs characteristic of captive rearing. These results have important implications for host adaptation to local selective pressures, and highlight how conditions experienced during early life can have a long-term influence on the microbiome and, potentially, host health.

Transcriptomic response to aquaculture intensification in Nile tilapia.

To meet future global demand for fish protein, more fish will need to be farmed using fewer resources, and this will require the selection of nonaggressive individuals that perform well at high densities. Yet, the genetic changes underlying loss of aggression and adaptation to crowding during aquaculture intensification are largely unknown. We examined the transcriptomic response to aggression and crowding in Nile tilapia, one of the oldest and most widespread farmed fish, whose social structure shifts from social hierarchies to shoaling with increasing density. A mirror test was used to quantify aggression and skin darkening (a proxy for stress) of fish reared at low and high densities, and gene expression in the hypothalamus was analysed among the most and least aggressive fish at each density. Fish reared at high density were darker, had larger brains, were less active and less aggressive than those reared at low density and had differentially expressed genes consistent with a reactive stress-coping style and activation of the hypothalamus-pituitary-interrenal (HPI) axis. Differences in gene expression among aggressive fish were accounted for by density and the interaction between density and aggression levels, whereas for nonaggressive fish differences in gene expression were associated with individual variation in skin brightness and social stress. Thus, the response to crowding in Nile tilapia is context dependent and involves different neuroendocrine pathways, depending on social status. Knowledge of genes associated with the response to crowding may pave the way for more efficient fish domestication, based on the selection of nonaggressive individuals with increasing tolerance to chronic stress necessary for aquaculture intensification.

Parasite biodiversity faces extinction and redistribution in a changing climate.

Climate change is a well-documented driver of both wildlife extinction and disease emergence, but the negative impacts of climate change on parasite diversity are undocumented. We compiled the most comprehensive spatially explicit data set available for parasites, projected range shifts in a changing climate, and estimated extinction rates for eight major parasite clades. On the basis of 53,133 occurrences capturing the geographic ranges of 457 parasite species, conservative model projections suggest that 5 to 10% of these species are committed to extinction by 2070 from climate-driven habitat loss alone. We find no evidence that parasites with zoonotic potential have a significantly higher potential to gain range in a changing climate, but we do find that ectoparasites (especially ticks) fare disproportionately worse than endoparasites. Accounting for host-driven coextinctions, models predict that up to 30% of parasitic worms are committed to extinction, driven by a combination of direct and indirect pressures. Despite high local extinction rates, parasite richness could still increase by an order of magnitude in some places, because species successfully tracking climate change invade temperate ecosystems and replace native species with unpredictable ecological consequences.

Predictive factors for oropharyngeal mycosis during radiochemotherapy for head and neck carcinoma and consequences on treatment duration. Results of mycosis in radiotherapy (MIR): a prospective longitudinal study.

BACKGROUND AND PURPOSE: Oropharyngeal mycosis (OPM) is a complication of radiotherapy (RT) treatments for head and neck (H&N) cancer, worsening mucositis and dysphagia, causing treatment interruptions and increasing overall treatment time. Prophylaxis with antifungals is expensive. Better patient selection through the analysis of prognostic factors should improve treatment efficacy and reduce costs. MATERIALS AND METHODS: A multicentre, prospective, controlled longitudinal study, with ethics committee approval, examined H&N cancer patients who were candidates for curative treatments with radio-chemotherapy. Patients were divided in groups according to OPM appearance: before the starting of RT (cases), during RT (new cases) and never (no cases). RESULTS: Of 410 evaluable patients, 20 were existing cases, 201 new cases and 189 did not report OPM. In our study OPM appears in 42.4% of people >70years and in 58.2% of younger individuals (p=0.0042), and in 68.6% of women versus 50.8% of men (p=0.0069). Mucositis and dysphagia were higher and salivation reduced among people with OPM (p<0.0000). Patients with OPM had longer hospitalization (p=0.0002) and longer (>12days) treatment interruptions (p=0.0288). CONCLUSIONS: Patients with OPM had higher toxicity and a greater number of long treatment interruptions. Analyses of prognostic factors can help clinicians understand OPM distribution and select patients with the highest probability of OPM for antifungal prophylaxis.

Comparative dosimetric and radiobiological assessment among a nonstandard RapidArc, standard RapidArc, classical intensity-modulated radiotherapy, and 3D brachytherapy for the treatment of the vaginal vault in patients affected by gynecologic cancer.

To evaluate a nonstandard RapidArc (RA) modality as alternative to high-dose-rate brachytherapy (HDR-BRT) or IMRT treatments of the vaginal vault in patients with gynecological cancer (GC). Nonstandard (with vaginal applicator) and standard (without vaginal applicator) RapidArc plans for 27 women with GC were developed to compare with HDR-BRT and IMRT. Dosimetric and radiobiological comparison were performed by means of dose-volume histogram and equivalent uniform dose (EUD) for planning target volume (PTV) and organs at risk (OARs). In addition, the integral dose and the overall treatment times were evaluated. RA, as well as IMRT, results in a high uniform dose on PTV compared with HDR-BRT. However, the average of EUD for HDR-BRT was significantly higher than those with RA and IMRT. With respect to the OARs, standard RA was equivalent of IMRT but inferior to HDR-BRT. Furthermore, nonstandard RA was comparable with IMRT for bladder and sigmoid and better than HDR-BRT for the rectum because of a significant reduction of d(2cc), d(1cc), and d(max) (p < 0.01). Integral doses were always higher than HDR-BRT, although the values were very low. Delivery times were about the same and more than double for HDR-BRT compared with IMRT and RA, respectively. In conclusion, the boost of dose on vaginal vault in patients affected by GC delivered by a nonstandard RA technique was a reasonable alternative to the conventional HDR-BRT because of a reduction of delivery time and rectal dose at substantial comparable doses for the bladder and sigmoid. However HDR-BRT provides better performance in terms of PTV coverage as evidenced by a greater EUD.

A case of thyroid metastasis of nasopharyngeal cancer.

AIMS AND BACKGROUND: Thyroid metastasis from nasopharyngeal carcinoma is a rare occurrence. We report a case of thyroid metastases from nasopharyngeal carcinoma with a review of the literature. METHODS: In April 2007 a 59-year-old man was diagnosed with nasopharyngeal carcinoma; in October 2009 he underwent a thyroid biopsy that revealed G2 infiltrating spinocellular carcinoma with lymph node involvement. He was treated with chemotherapy and radiotherapy at our institute. RESULTS: Currently, after 6 cycles of adjuvant chemotherapy with taxotere and gemcitabine, the patient is asymptomatic with stable disease and improved quality of life. CONCLUSION: According to the literature, the treatment choice depends on clinical disease extent. Surgery and/or chemo-radiation therapy must therefore be tailored to the individual patient in order to improve clinical outcome and quality of life.