Immunonutrition, Metabolism, and Programmed Cell Death in Lung Cancer: Translating Bench to Bedside.

Lung cancer presents significant therapeutic challenges, motivating the exploration of novel treatment strategies. Programmed cell death (PCD) mechanisms, encompassing apoptosis, autophagy, and programmed necrosis, are pivotal in lung cancer pathogenesis and the treatment response. Dysregulation of these pathways contributes to tumor progression and therapy resistance. Immunonutrition, employing specific nutrients to modulate immune function, and metabolic reprogramming, a hallmark of cancer cells, offer promising avenues for intervention. Nutritional interventions, such as omega-3 fatty acids, exert modulatory effects on PCD pathways in cancer cells, while targeting metabolic pathways implicated in apoptosis regulation represents a compelling therapeutic approach. Clinical evidence supports the role of immunonutritional interventions, including omega-3 fatty acids, in augmenting PCD and enhancing treatment outcomes in patients with lung cancer. Furthermore, synthetic analogs of natural compounds, such as resveratrol, demonstrate promising anticancer properties by modulating apoptotic signaling pathways. This review underscores the convergence of immunonutrition, metabolism, and PCD pathways in lung cancer biology, emphasizing the potential for therapeutic exploration in this complex disease. Further elucidation of the specific molecular mechanisms governing these interactions is imperative for translating these findings into clinical practice and improving lung cancer management.

Postoperative Hypofractionated Radiotherapy for Prostate Cancer.

AIM: To retrospectively investigate outcomes, and acute and late complications following postoperative hypofractionated 3D conformal radiotherapy. PATIENTS AND METHODS: Sixty-nine consecutive patients underwent radical prostatectomy. Radiotherapy was delivered to the prostatic fossa by means of a7-fieldLINACwith 6-15 MV to a total dose of 62.5 Gy in 25 fractions (2.5 Gy per fraction) in five consecutive weeks. RESULTS: Median follow-up was 54.7 months (range=38-76 months). Five-year overall survival, metastasis-free survival and biochemical relapse-free survival were 91.1%, 84.6% and 66.7%, respectively. Grade 2 or more genitourinary and gastrointestinal acute toxicity was reported in 12% and 5% of patients, respectively. Urinary incontinence grade 2 or more was recorded in 19%. CONCLUSION: Postoperative radiotherapy either in the adjuvant or salvage setting resulted in acceptable rates of acute and late toxicity with good tumor control while reducing overall treatment time. Confirmatory results from an ongoing prospective trial are awaited.

Hypofractionated Dose Escalated 3D Conformal Radiotherapy for Prostate Cancer: Outcomes from a Mono-Institutional Phase II Study.

BACKGROUND/AIM: Based on a radiobiological assumption of a low alpha/beta (α/ß) ratio for prostate cancer, hypofractionated radiotherapy has increasingly gained traction in the clinical practice and recent guidelines have confirmed the non-inferiority of this approach. Nevertheless, the largest studies that have used hypofractionation so far, employed image-guided radiation therapy/intensity modulated radiation therapy (IGRT/IMRT) facilities that might have overcome the radiobiological advantages, which remain to be fully confirmed. The aim of this trial was to evaluate the feasibility of a hypofractionated schedule delivered with 3D-Conformal Radiotherapy to prostate and seminal vesicles in combination with hormonal therapy. PATIENTS AND METHODS: The study included 97 consecutive patients with localized prostate cancer (PCa), irrespective of risk class, treated with a schedule of 62 Gy in 20 fractions over 5 weeks (4 fractions of 3.1 Gy each per week). According to National Comprehensive Cancer Network (NCCN) prognostic classification, patients were divided into a favourable group (19%), intermediate group (41%) and unfavourable group (40%). Early and late toxicities were scored using the radiation toxicity grading/European Organisation for Research and Treatment of Cancer (RTOG/EORTC) criteria. Additionally, the international prostate symptom index (IPSS) for benign prostate hypertrophy was used to evaluate obstructive urinary symptoms. Biochemical outcome was reported according to the Phoenix definition for biochemical failure. Hormonal therapy (HT) was administrated in 92% of patients. RESULTS: After a median follow-up of 39 months (range=25-52), maximum ≥G2 late genitourinary (GU) and gastrointestinal (GI) toxicities occurred in 8% and 11% patients, respectively. The corresponding figures for acute toxicities were 24% and 15%. Patients with higher IPSS score before enrolment had significantly worse urinary function after treatment. Only 2% of patients died from PCa. Biochemical non-evidence of disease (bNED) was 83% for all patients. CONCLUSION: Our study confirms that 3D conformal radiotherapy (3DCRT) remains a safe and effective method to deliver a dose-escalated hypofractionated regimen for PCa patients in all risk classes with acceptable toxicity rates and optimal biochemical control.

High-dose 3D-CRT in the radical and postoperative setting for prostate cancer. Analysis of survival and late rectal and urinary toxicity.

PURPOSE: The aim of the study was to retrospectively compare outcome and complications of prostate cancer patients treated with a curative and postoperative intent using a pretreatment defined NCCN classification. MATERIAL AND METHODS: A total of 103 patients was treated curatively (RAD) and 94 postoperatively (POST-OP). The mean age was higher in the RAD group (72.6 years; range, 56.4-85.1) than in the POST-OP group (65.4 years; range, 43.9-77) (P <0.0001). According to the NCCN prognostic classification, 13 (12%) patients were at low risk, 48 (47%) at intermediate risk and 42 (41%) at high risk in the RAD group. In the POST-OP group, 13 (14%) patients were low risk, 37 (40%) at intermediate risk and 44 (46%) at high risk. Hormone therapy was used in 98 patients (95%) in the RAD group and 45 patients (47.8%) in the POST-OP group. Patients were treated with three-dimensional conformal radiotherapy. The prescription dose was 80 Gy in 2-Gy fractions in the RAD group and 70 Gy in 2-Gy fractions in the POST-OP. RESULTS: No biochemical, clinical relapse was found in low-risk patients in the RAD group and 1 relapse was found in the POST-OP group. The largest number of relapses occurred (39%) and (33%) in intermediate-high risk in RAD and POST-OP groups, respectively. In the cause-specific survival analysis, no significant differences were found in the high-risk group between RAD and POST-OP groups (P = 0.9). In the analysis of 5-year biochemical relapse-free survival, no significant differences were found in the high-risk group between RAD and POST-OP groups (P = 0.1020). CONCLUSIONS: Radiotherapy in the RAD low-risk group was an excellent treatment. RAD and POST-OP radiotherapy were well tolerated with very low toxicity. The cause-specific survival at 5 years was 95% and 97% for the two treatment groups, RAD and POST-OP, respectively (logrank test, P = 0.2908).

Oral mucosal color changes as a clinical biomarker for cancer detection.

Screening is a key tool for early cancer detection/prevention and potentially saves lives. Oral mucosal vascular aberrations and color changes have been reported in hereditary nonpolyposis colorectal cancer patients, possibly reflecting a subclinical extracellular matrix abnormality implicated in the general process of cancer development. Reasoning that physicochemical changes of a tissue should affect its optical properties, we investigated the diagnostic ability of oral mucosal color to identify patients with several types of cancer. A total of 67 patients with several histologically proven malignancies at different stages were enrolled along with a group of 60 healthy controls of comparable age and sex ratio. Oral mucosal color was measured in selected areas, and then univariate, cluster, and principal component analyses were carried out. Lower red and green and higher blue values were significantly associated with evidence of cancer (all P<0.0001), and efficiently discriminated patients from controls. The blue color coordinate showed significantly higher sensitivity and specificity (96.66±2.77 and 97.16±3.46%, respectively) compared with the red and green coordinates. Likewise, the second principal component coordinate of the red-green clusters discriminated patients from controls with 98.2% sensitivity and 95% specificity (cut-off criterion≤0.4547; P=0.0001). The scatterplots of the chrominances revealed the formation of two well separated clusters, separating cancer patients from controls with a 99.4% probability of correct classification. These findings highlight the ability of oral color to encode clinically relevant biophysical information. In the near future, this low-cost and noninvasive method may become a useful tool for early cancer detection.

Analysis of survival in radical and postoperative radiotherapy for prostate cancer.

PURPOSE: To analyze survival and complications in high dose 3D conformal radiotherapy (3DCRT) patients treated with curative and post-operative intent and compare radical surgery + radiotherapy (RT) patients vs. RT only patients. MATERIAL AND METHOD: 103 patients were treated curatively (RAD), 94 postoperatively (POST-OP). The mean age was higher in RAD group (72.6 years, range 56.4-85.1) than in POST-OP group (65.4 years, 43.9-77) (p < 0.0001). According to NCCN prognostic classification 13 (12%) patients was low risk, 48 (47%) intermediate risk and 42 (41%) high risk in RAD group. In POST-OP group 13 (14%) patients were low risk, 37 (40%) intermediate risk and 44 (46%) high risk. Hormone Therapy (HT) was administered in 98 patients (95%) in RAD and in 45 patients (47.8%) in POST-OP. Patients were treated with a three-dimensional conformal radiotherapy (3D-CRT). In RAD 15 (15%) were alive with disease (AWD), 5 (5%) dead of disease (DOD) and 10 (10%) dead of other cause (DOC); in POST-OP 14 (14.8%) were AWD, 2 (2%) DOD and 3 (3%) DOC. The prescription dose was 80 Gy in 2-Gy fractions in the RAD group, and 70 Gy in 2-Gy fractions in the POST-OP, respectively. RESULTS: No biochemical or clinical relapse was found in low risk patients in RAD group and 1 relapse in POST-OP group. The largest number of relapses occurred and in intermediate-high risk in RAD (39%) and POST-OP group (33%). In the cause-specific survival analysis no significant differences were found in high risk group between RAD and POST-OP (p = 0.9). In the biochemical relapse-free survival (bRFS) at 5 years analysis no significant differences were found in the high risk group between RAD and POST-OP (p = 0.1020). CONCLUSION: RT in RAD low- risk is very effectiva. RAD and POST-OP RT were well tolerated with a very low toxicity. The cause-specific survival at 5 years was 95% and 97% for the two groups of treatment, RAD and POST-OP respectively (Log-rank test p = 0.2908).