Chemotherapy-induced early transient increase and surge of CA 19-9 level in patients with pancreatic Adenocarcinoma✰.

This study aimed to characterize chemotherapy-induced transient increase and surge of CA 19-9 level to treatment response in patients with advanced pancreatic ductal adenocarcinoma (PDAC). A retrospective case series was performed of advanced PDAC patients treated with first-line chemotherapy at City of Hope Comprehensive Cancer Center from Jan 2017 to May 2020. CA 19-9 surge was defined as an increase of >20% from baseline followed by a >20% drop in one or more subsequent CA 19-9 levels compared to baseline. Out of 106 advanced PDAC patients, 38 were evaluable for CA 19-9 surge. Fourteen (51.9%) patients treated with FOLFIRINOX and 3 (27.3%) patients treated with nab-P + Gem chemotherapy demonstrated an early transient rise in CA 19-9 level. A CA 19-9 surge was documented in 9 (23.7%) patients, all with duration of surge lasting < 16 weeks. Five out of 9 (55.6%) patients (4: FOLFIRINOX, 1: nab-P + Gem) with CA 19-9 surge demonstrated partial objective response rate on surveillance cross-sectional imaging. One patient (FOLFIRINOX) had stable disease, and 2 patients (1: FOLFIRINOX, 1: nab-P + Gem) were found to have disease progression after treatment interruption. The initial early rise of CA 19-9 levels during chemotherapy in patients with advanced PDAC may not indicate tumor progression. Rather, it may represent a chemotherapy-induced transient increase or surge phenomenon of the tumor marker in patients responding to treatment.

Parenteral glutamine supplementation improves serum albumin values in surgical cancer patients.

INTRODUCTION: Patients with gastric adenocarcinoma (GA) often develop malnutrition, which deteriorates after cancer surgery and negatively affects surgical outcomes. Despite being an abundant and versatile amino acid involved in the immune system and metabolic functions, glutamine levels are significantly depleted among patients who are critically ill or hypercatabolic. Therefore, this study aimed to investigate whether parenteral glutamine supplementation may improve nutritional status and surgical outcomes. METHODS: This retrospective, single-center cohort study included patients with GA who underwent gastrectomy between January 2007 and June 2019. Patients were classified into either the non-glutamine or glutamine group. Propensity score matching was used to minimize the bias in patient demographics. Furthermore, the average parenteral glutamine dose from the day of surgery to postoperative day four was calculated in g/kg/day. Surgical outcomes (length of hospitalization, major complication, and mortality) and changes in lymphocyte count and serum albumin levels 7 days post-surgery were assessed in both matched groups using adjusted models. RESULTS: A total of 1950 patients were reviewed, among whom 522 (26.8%) received parenteral glutamine supplementation (glutamine dose ranging from 0.05 to 0.49 g/kg/day). Among the included patients, 57.2% were males, and the median age was 64.9 years. After matching, there were 478 cases in each group. No differences in surgical outcomes and changes in lymphocyte count were observed between both matched groups. The glutamine group exhibited a smaller decrease in serum albumin levels compared to the non-glutamine group (-0.6 vs. -1.1 g/dL; P < 0.001). The adjusted matched model showed that glutamine dose contributed significantly toward increasing serum albumin levels (coefficient = 0.08 per 0.1 g/day/kg increment in glutamine; 95% confidence interval: 0.04 to 0.10; P < 0.001). CONCLUSIONS: Perioperative parenteral glutamine supplementation had a positive dose-dependent impact on the recovery of serum albumin levels among patients with GA undergoing gastrectomy, implying that glutamine supplementation improved postoperative nutritional suppression and ameliorated stress-associated inflammation. Although glutamine supplementation was not associated with surgical outcomes, further studies should be conducted to evaluate the clinical significance of serum albumin restoration.

Prognostic Value of Pretreatment Serum CA199 in Patients with Locally Advanced Rectal Cancer Treated with CRT Followed by TME with Normal Pretreatment Carcinoembryonic Antigen Levels.

BACKGROUND: Elevated pretreatment carcinoembryonic antigen (CEA) levels are related to poor prognosis in patients with locally advanced rectal cancer (LARC) treated with neo-CRT followed by TME. In patients with normal pretreatment CEA levels, the prognostic significance of carbohydrate antigen 199 (CA199) is controversial. OBJECTIVES: The aim of this study was to explore the prognostic value of pretreatment serum CA199 in patients with LARC who had normal pretreatment CEA levels treated with neo-CRT followed by curative surgery. METHODS: A retrospective study of 456 patients with LARC treated with neo-CRT followed by TME between January 2006 and May 2017 was performed. We employed the maximal χ2 method to determine the CA199 threshold of 9.1 U/mL based on the difference in survival and divided patients into 2 groups. Group 1: patients with pretreatment s-CEA < 5 ng/mL and CA199 ≥ 9.1 U/mL. Group 2: patients with pretreatment s-CEA < 5 ng/mL and CA199 < 9.1 U/mL. Overall survival (OS) across CA199 was assessed using Cox proportional hazard regression models (PS:CEA ≥ 5 ng/mL was seen as elevated). RESULTS: Multivariate analyses demonstrated that the following factors were significantly related to OS in patients with LARC with normal pretreatment CEA levels: ypT (odds ratio [OR] 1.863, p = 0.030), ypN (OR 1.622, p = 0.026), and pretreatment CA199 levels (OR 1.886, p = 0.048). CONCLUSION: Pretreatment CA199 is an independent factor for OS in patients with LARC with normal pretreatment CEA levels, which may reach the clinic to guide individualized decision-making.

Linac-based stereotactic body radiation therapy for low and intermediate-risk prostate cancer : Long-term results and factors predictive for outcome and toxicity.

INTRODUCTION: Stereotactic body radiation therapy (SBRT) is considered an effective and safe treatment in patients with low- and intermediate-risk prostate cancer (PC). However, due to a lack of long-term follow-up and late toxicity data, this treatment is not universally accepted. The present study aimed to evaluate outcome and early and late toxicity in a cohort of patients with low- and intermediate-risk PC treated prospectively with linear accelerator (linac)-based SBRT. PATIENTS AND METHODS: Patients with low- or intermediate-risk (NCCN criteria) PC were included. All patients received linac-based SBRT to 35 Gy in 5 fractions delivered on alternate days. Endpoints were toxicity, biochemical relapse-free survival (BRFS), metastatic progression-free survival (mPFS), and overall survival (OS). RESULTS: From 2012 to 2018, 178 patients were treated. Median baseline prostate-specific antigen (iPSA) was 6.37 ng/ml (range 1.78-20). Previous transurethral resection of the prostate (TURP) was present in 23 (12.9%) patients. Median follow-up was 58.9 months (range 9.7-89.9). BRFS rates at 1, 3, and 5 years were 98.3 (95% confidence interval, CI, 94.7-99.4%), 94.4 (95%CI 89.4-97), and 91.6% (95%CI 85.4-95.2), respectively. In univariate analysis, performance status (PS), iPSA, and nadir PSA (nPSA) were correlated with BRFS. In multivariable analysis iPSA and nPSA remained significant. BRFS rates at 5 years were 94.9% (95%CI 86.8-98) for International Society of Urological Pathology (ISUP) grade group 1, 93.2% (95%CI 80.5-97.7) for ISUP group 2, and 74.8% (95%CI 47.1-89.5) for ISUP group 3. At 1, 3, and 5 years, mPFS rates were 98.8 (95%CI 95.5-99.7), 96.2 (95%CI 91.9-98.3), and 92.9% (95%CI 87.2-96.2), respectively; OS rates were 100, 97.2 (95%CI 92.9-98.9), and 95.1% (95%CI 90-97.6), respectively. One (0.56%) case of grade 3 acute genitourinary (GU), one case of acute gastrointestinal (GI), and one case of grade 3 late GU toxicity were observed. GI toxicity positively correlated with prostate volume. CONCLUSION: At long-term follow-up, linac-based SBRT continues to be a valid option for the management localized PC. Biochemical control remains high at 5 years, albeit with some concerns regarding the optimal schedule for unfavorable intermediate-risk PC. Considering the excellent prognosis, patient selection is crucial for prevention of severe late toxicity.

High prevalence of severe hypovitaminosis D in patients with advanced gastric cancer treated with first-line chemotherapy with or without anti-EGFR-directed monoclonal antibody (EXPAND trial) showing no prognostic impact.

PURPOSE: The goal of our analysis was to study pretherapeutic circulating 25-OHD plasma levels in patients with previously untreated advanced gastric cancer treated in the randomised controlled phase III Erbitux (cetuximab) in combination with Xeloda (capecitabine) and cisplatin in advanced esophago-gastric cancer (EXPAND) trial (NCT00678535) and to explore whether low 25-OHD plasma levels are associated with worse prognosis and may compromise the clinical efficacy of cetuximab. METHODS: Six hundred thirty patients with available pretherapeutic 25-OHD plasma levels and treated with chemotherapy based on capecitabine and cisplatin, or chemotherapy and cetuximab, were included. The Cox proportional hazard regression model was used to analyse the association between low 25-OHD and survival in both treatment arms. RESULTS: Majority of study patients were found to have severe vitamin D deficiency. No prognostic impact of 25-OHD plasma levels could be found in our patient cohort, and there was no indication of an interference of 25-OHD plasma levels and the efficacy of treatment with the anti-epidermal growth factor receptor monoclonal antibody cetuximab. CONCLUSIONS: Although majority of patients with advanced gastric cancer show hypovitaminosis D deficiency, there is no proof for a negative impact on survival or reduced treatment response. A prospective study is needed to investigate the potential benefit of vitamin D supplementation in this patient cohort during first-line chemotherapy.

Novel Prognostic Factors in Resected Small Bowel Adenocarcinoma.

BACKGROUND: Small bowel adenocarcinoma (SBA) is a rare malignancy affecting approximately 3000 patients per year in the United States, and there is limited evidence prognosticating patients with resected SBA. We aimed to evaluate prognostic factors and the role of adjuvant therapy in patients with resected SBA. PATIENTS AND METHODS: Two hundred forty-one patients who had resected stage I-III SBA were retrospectively identified at a single tertiary referral institution. Overall survival (OS) analysis was performed by the Kaplan-Meier method, and Wilcoxon tests were used for statistical comparisons. Cox proportional hazards were performed to identify significant variables by univariate and multivariate analysis. RESULTS: Median OS for the entire group was 54.5 months (95% confidence interval [CI], 37.2-81.2 months), with 5- and 10-year OS of 48% and 35%. Median follow-up was 113.7 months (95% CI, 97.9-126.6 months). For patients with stage III disease who received adjuvant therapy, the median OS was 33.8 months (95% CI, 27.8-78.8) compared to 24.7 months (95% CI, 11.5-37.8) for patients with no adjuvant therapy (P < .01). Male sex, advanced T stage, advanced N stage, increased positive lymph node ratio, lymphocyte-to-monocyte ratio < 1.56, presence of residual disease, and earlier date of diagnosis predicted worse survival on univariate analysis. Age > 60 years, lymphocyte-to-monocyte ratio < 1.56, and advanced T stage were identified as independent negative predictors of OS for all patients by multivariate analysis. CONCLUSION: Advanced age, advanced T stage, and lymphocyte-to-monocyte ratio < 1.56 independently predicted survival in resected SBA. Adjuvant therapy is associated with improved survival in patients with resected stage III SBA.

Improvement of chemotherapy through reducing of cachexia by using Citrus unshiu peel extract.

ETHNOPHARMACOLOGICAL RELEVANCE: .Colorectal cancer (CRC) is now one the fourth cause of mortality and morbidity due to cancer throughout the globe. Cachexia is more prevalent in patients with this cancer and has a negative effect on response to chemotherapy and radiotherapy. Inflammatory cytokines such as TNF-α, IL-1ß, and IL-6 could play a key role in cachexia. Moreover strong chemotherapy medications such as doxorubicin have complications such as toxicity and cachexia. Citrus unshiu Peel have been used as traditional herbal drugs for the treatment of cancer in traditional oriental medicine (TOM). Since its main components have anti-inflammatory effects, we evaluated the anti-cachexia activity in order to support the traditional usage of Citrus unshiu peel. Aim of the study; We aimed to assess the preventive or therapeutic effect of Citrus unshiu Peel Extract (CUPE) on cachexia by reducing of inflammatory cytokines in mice bearing C26 tumor. Also the contribution role of CUPE has evaluated on improvement of chemotherapy through reducing of inflammatory cytokines. Materials and Methods; The CUPE was prepared by Soxhlet extractor and quantitative and qualitative analysis of aqua extract was performed by high performance liquid chromatography (HPLC). C26 tumor bearing BALB/c male mice were immunized with different formulation of oral Prophylactic-therapeutic CUPE and/or intraperitoneal doxorubicin and then were monitored for weight gain, food intake and tumor size throughout the study. On the 32nd day after tumor injection, inflammatory cytokines levels, IL6, TNF-α and IL-1ß were evaluated by Enzyme-linked Immunosorbent Assay (ELISA) and Malondialdehyde- Thiobarbituric acid (MDA) levels were measured by standard method. Results; Oral administration of CUPE in both prophylactic and therapeutic formulation to C26 adenocarcinoma bearing mice reduced the weight loss, tumor volume, and serum MDA levels compared with untreated tumor-bearing mice and Doxorubicin (Dox) groups. Also, the combination therapy of (CUPE + Dox) leads to reducing the levels of serum IL-6, TNF-α, IL-1ß and tumor volume compared with untreated tumor-bearing mice and Dox groups. Serum MDA levels were considerably reduced by combination therapy of (CUPE + Dox) compared with Dox groups. Conclusions; These findings confirm the safety and efficacy of CUPE on C26 adenocarcinoma bearing mice as pure and adjuvant therapy, the results of which might be used in further human studies as a valuable natural anticancer agent alone or in combination with chemotherapy. Also the results showed that simultaneous application of CUPE and Dox leads to significant reduction of cachexia from the Dox chemotherapy.

Evaluation of Intense Androgen Deprivation Before Prostatectomy: A Randomized Phase II Trial of Enzalutamide and Leuprolide With or Without Abiraterone.

PURPOSE: Patients with locally advanced prostate cancer have an increased risk of cancer recurrence and mortality. In this phase II trial, we evaluate neoadjuvant enzalutamide and leuprolide (EL) with or without abiraterone and prednisone (ELAP) before radical prostatectomy (RP) in men with locally advanced prostate cancer. PATIENTS AND METHODS: Eligible patients had a biopsy Gleason score of 4 + 3 = 7 or greater, prostate-specific antigen (PSA) greater than 20 ng/mL, or T3 disease (by prostate magnetic resonance imaging). Lymph nodes were required to be smaller than 20 mm. Patients were randomly assigned 2:1 to ELAP or EL for 24 weeks followed by RP. All specimens underwent central pathology review. The primary end point was pathologic complete response or minimal residual disease (residual tumor ≤ 5 mm). Secondary end points were PSA, surgical staging, positive margins, and safety. Biomarkers associated with pathologic outcomes were explored. RESULTS: Seventy-five patients were enrolled at four centers. Most patients had high-risk disease by National Comprehensive Cancer Network criteria (n = 65; 87%). The pathologic complete response or minimal residual disease rate was 30% (n = 15 of 50) in ELAP-treated patients and 16% (n = four of 25) in EL-treated patients (two-sided P = .263). Rates of ypT3 disease, positive margins, and positive lymph nodes were similar between arms. Treatment was well-tolerated. Residual tumors in the two arms showed comparable levels of ERG, PTEN, androgen receptor PSA, and glucocorticoid receptor expression. Tumor ERG positivity and PTEN loss were associated with more extensive residual tumors at RP. CONCLUSION: Neoadjuvant hormone therapy followed by RP in locally advanced prostate cancer resulted in favorable pathologic responses in some patients, with a trend toward improved pathologic outcomes with ELAP. Longer follow-up is necessary to evaluate the impact of therapy on recurrence rates. The potential association of ERG and PTEN alterations with worse outcomes warrants additional investigation.

C-Reactive Protein Level Predicts Survival Outcomes in Rectal Cancer Patients Undergoing Total Mesorectal Excision After Preoperative Chemoradiation Therapy.

BACKGROUND: Systemic inflammatory response, as measured by C-reactive protein (CRP), is associated with prognosis in various types of human malignancies. However, to the best of our knowledge, the clinical significance of CRP in patients with locally advanced rectal cancer that undergo preoperative chemoradiation has not been investigated in detail. This retrospective study validates CRP as a potential predictive marker for survival outcomes in rectal cancer patients. METHODS: In this study, we enrolled 125 patients that received total mesorectal excision after preoperative chemoradiation for rectal cancer between January 2003 and December 2010. We investigated the association between preoperative CRP and clinicopathological characteristics and assessed the prognostic value of CRP. RESULTS: The median follow-up was 41 months. Elevated CRP showed significant correlation with high histological grade (P = 0.009) and cancer recurrence (P = 0.027). The 5-year disease-free survival and cancer-specific survival were significantly lower in the elevated CRP group (P = 0.001). Moreover, CRP was the strongest predictive factor for cancer-specific survival in multivariate analysis (P = 0.001). In the subgroup analysis, elevated CRP was a significant prognostic factor in patients with node-positive disease (P = 0.025) and was associated with poorer tumor regression (TRG4-5; P = 0.011). CONCLUSIONS: The results of our study suggest that preoperative CRP level shows prognostic significance in rectal cancer patients that have undergone chemoradiation. Therefore, preoperative CRP may help clinicians to identify patients that need additional therapy to reduce systemic failure.

PROstate Multicentre External beam radioTHErapy Using a Stereotactic boost: the PROMETHEUS study protocol.

BACKGROUND: High Dose Rate Brachytherapy (HDRB) boost is a well-established treatment for prostate cancer (PC). We describe the PROstate Multicentre External beam radioTHErapy Using Stereotactic boost (PROMETHEUS) study. Non-surgical stereotactic techniques are used to deliver similar doses to HDRB boost regimens with a dose escalation sub-study. METHODS: Eligible patients have intermediate or high risk PC. PROMETHEUS explores the safety, efficacy and feasibility of multiple Australian centres cooperating in the delivery of Prostate Stereotactic Body Radiotherapy (SBRT) technology. A SBRT boost component Target Dose (TD) of 19Gy in two fractions is to be delivered, followed by a subsequent EBRT component of 46Gy in 23 fractions. Once accrual triggers have been met, SBRT doses can be escalated in 1 Gy increments to a maximum of 22Gy in two fractions. Patient safety will also be measured with the rate of both acute and late moderate to severe Gastro-Intestinal (GI) and Genito-Urinary (GU) Common Terminology Criteria for Adverse Events (CTCAE) toxicities as well as patient reported quality of life. Efficacy will be assessed via biochemical control after 3 years. DISCUSSION: PROMETHEUS aims to generate evidence for a non-surgical possible future alternative to HDRB boost regimens, and introduce advanced radiotherapy techniques across multiple Australian cancer centres. TRIAL REGISTRATION: The study was retrospectively registered on the ANZCTR (Australian New Zealand Clinical Trials Registry) with trial ID: ACTRN12615000223538 .

Clinical Application of Genomic Profiling With Circulating Tumor DNA for Management of Advanced Non-Small-cell Lung Cancer in Asia.

BACKGROUND: Genomic profiling of cell-free circulating tumor DNA (ctDNA) is a potential alternative to repeat invasive biopsy in patients with advanced cancer. We report the first real-world cohort of comprehensive genomic assessments of patients with non-small-cell lung cancer (NSCLC) in a Chinese population. PATIENTS AND METHODS: We performed a retrospective analysis of patients with advanced or metastatic NSCLC whose physician requested ctDNA-based genomic profiling using the Guardant360 platform from January 2016 to June 2017. Guardant360 includes all 4 major types of genomic alterations (point mutations, insertion-deletion alterations, fusions, and amplifications) in 73 genes. RESULTS: Genomic profiling was performed in 76 patients from Hong Kong during the 18-month study period (median age, 59.5 years; 41 men and 35 women). The histologic types included adenocarcinoma (n = 10), NSCLC, not otherwise specified (n = 58), and squamous cell carcinoma (n = 8). In the adenocarcinoma and NSCLC, not otherwise specified, combined group, 62 of the 68 patients (91%) had variants identified (range, 1-12; median, 3), of whom, 26 (42%) had ≥ 1 of the 7 National Comprehensive Cancer Network-recommended lung adenocarcinoma genomic targets. Concurrent detection of driver and resistance mutations were identified in 6 of 13 patients with EGFR driver mutations and in 3 of 5 patients with EML4-ALK fusions. All 8 patients with squamous cell carcinoma had multiple variants identified (range, 1-20; median, 6), including FGFR1 amplification and ERBB2 (HER2) amplification. PIK3CA amplification occurred in combination with either FGFR1 or ERBB2 (HER2) amplification or alone. CONCLUSION: Genomic profiling using ctDNA analysis detected alterations in most patients with advanced-stage NSCLC, with targetable aberrations and resistance mechanisms identified. This approach has demonstrated its feasibility in Asia.

Association of Preoperative and Postoperative Serum Carcinoembryonic Antigen and Colon Cancer Outcome.

IMPORTANCE: Guidelines recommend measuring preoperative carcinoembryonic antigen (CEA) in patients with colon cancer. Although persistently elevated CEA after surgery has been associated with increased risk for metastatic disease, prognostic significance of elevated preoperative CEA that normalized after resection is unknown. OBJECTIVE: To investigate whether patients with elevated preoperative CEA that normalizes after colon cancer resection have a higher risk of recurrence than patients with normal preoperative CEA. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort analysis was conducted at a comprehensive cancer center. Consecutive patients with colon cancer who underwent curative resection for stage I to III colon adenocarcinoma at the center from January 2007 to December 2014 were identified. EXPOSURES: Patients were grouped into 3 cohorts: normal preoperative CEA, elevated preoperative but normalized postoperative CEA, and elevated preoperative and postoperative CEA. MAIN OUTCOMES AND MEASURES: Three-year recurrence-free survival (RFS) and hazard function curves over time were analyzed. RESULTS: A total of 1027 patients (461 [50.4%] male; median [IQR] age, 64 [53-75] years) were identified. Patients with normal preoperative CEA had 7.4% higher 3-year RFS (n = 715 [89.7%]) than the combined cohorts with elevated preoperative CEA (n = 312 [82.3%]) (P = .01) but had RFS similar to that of patients with normalized postoperative CEA (n = 142 [87.9%]) (P = .86). Patients with elevated postoperative CEA had 14.9% lower RFS (n = 57 [74.5%]) than the combined cohorts with normal postoperative CEA (n = 857 [89.4%]) (P = .001). The hazard function of recurrence for elevated postoperative CEA peaked earlier than for the other cohorts. Multivariate analyses confirmed that elevated postoperative CEA (hazard ratio [HR], 2.0; 95% CI, 1.1-3.5), but not normalized postoperative CEA (HR, 0.77; 95% CI, 0.45-1.30), was independently associated with shorter RFS. CONCLUSIONS AND RELEVANCE: Elevated preoperative CEA that normalizes after resection is not an indicator of poor prognosis. Routine measurement of postoperative, rather than preoperative, CEA is warranted. Patients with elevated postoperative CEA are at increased risk for recurrence, especially within the first 12 months after surgery.

Circulating cell-free DNA as predictor of treatment failure after neoadjuvant chemo-radiotherapy before surgery in patients with locally advanced rectal cancer.

Background: Treatment of patients with locally advanced rectal cancer (LARC) is based on a combination of chemo-radiotherapy (CRT) and surgery. The rate of distant recurrences remains over 25%. Circulating cell-free DNA (cfDNA) in plasma is a mixture of normal and cancer-specific DNA segments and is a promising biomarker in patients with colorectal cancer. The aim of our study was to investigate plasma cfDNA as a prognostic marker for outcome in patients with LARC treated with neoadjuvant CRT and surgery. Patients and methods: In total, 123 patients with LARC were included in 2 biomarker studies. Patients were treated with neoadjuvant CRT before TME surgery. Fifty-two (42%) of the patients received induction chemotherapy with capecitabine + oxaliplatin. Total cfDNA was measured by direct fluorescent assay in EDTA plasma samples obtained at baseline, after induction chemotherapy, and after CRT. Serial samples 5 years after surgery were collected in 51 patients (41%). Results: Median follow-up was 55 months. Distant or local recurrence was seen in 30.9% of the patients. Patients with baseline cfDNA levels above the 75th quartile had a higher risk of local or distant recurrence and shorter time to recurrence compared with patients with plasma cfDNA below the 75th percentile (HR = 2.48, 95% CI: 1.3-4.8, P = 0.007). The same applied to disease-free survival (DFS) (HR = 2.43, 95% CI: 1.27-4.7, P = 0.015). In multivariate analysis, a high cfDNA level was significantly associated with time to progression and DFS. During follow-up, the association remained significant regardless of time point for sample analysis. Conclusion: We have demonstrated an association between a high baseline plasma level of cfDNA and increased risk of recurrence, shorter time to recurrence, and shorter DFS in patients with LARC. Consequently, cfDNA could potentially improve pre- and post-treatment risk assessment and facilitate individualized therapy for patients with LARC.

Value of post-therapy 177Lu-PSMA images for accurate interpretation of therapy response with 68Ga-PSMA PET/CT. / Valor de las imágenes de 177Lu-PSMA post-terapia para una interpretación precisa de la respuesta a la terapia con PET/TC con 68Ga-PSMA.

A 54-year-old man with progressive prostate cancer underwent a 68Ga-PSMA PET/CT, which showed lymph node and bone metastases. After 2-cycles of 177Lu-PSMA therapy, the repeated 68Ga-PSMA PET/CT showed decreased radiotracer uptake in lymph node and bones metastases, but there were new lesions which may be compatible with progression or tumour sink-effect. A review of 177Lu-PSMA-therapy images revealed that new lesions in the second PET/CT were the metastatic lesions that progressed after the first PET/CT, and subsequently showed a good response. The patient received additional cycles of 177Lu-PSMA therapy, and the disease regressed further, with a PSA of 0.06ng/ml. Response evaluation of new therapeutic diagnostics (theranostic) agents needs a review of not only diagnostic PET/CT images, but also post-therapy images and laboratory results.

Synchronous colorectal cancer and multiple myeloma with chest wall involvement: Is this a coincidence?

Multiple primary malignant neoplasms (MPMNs) are rare malignant neoplasms that simultaneously or successively occur in the same patient as 2 or more primary malignancies. Currently, an increasing number of cases are being reported. In general, MPMNs more commonly occur as 2 solid tumors or 2 hematological malignancies. Cases of MPMN that involve a solid tumor and a hematological malignancy are rare. Here, we report a case of synchronous colorectal cancer (CRC) and multiple myeloma (MM) with chest wall involvement. After reviewing the literature, we believe that there may be a distinct syndrome involving CRC and MM. The patient in our case study suffered refractory anemia following surgery and 2 cycles of chemotherapy. Initially, the anemia was considered to be a common manifestation of CRC in this patient. Interestingly, although he received a blood transfusion, his hemoglobin levels remained low. He later developed hematuria, proteinuria, multiple osteoporosis in the costal bones, and thrombocytopenia. These new symptoms drew our attention, and we considered a diagnosis of synchronous primary CRC and MM, with the anemia as a symptom of MM. Based on the results of a bone marrow aspirate, MM was confirmed. Therefore, when CRC is associated with refractory anemia, we should not only assume that anemia is a classical symptom of CRC, a result of chronic blood loss, nutritional deficiencies, or myelosuppression due to chemotherapy, but we should also consider that it may reflect the possibility of a coexisting hematologic malignancy. As the treatment of these 2 malignancies is different, early diagnosis and treatment based on definitive diagnosis as early as possible will be beneficial to overall prognosis.

Serum 25-hydroxyvitamin D concentrations and lung cancer risk in never-smoking postmenopausal women.

PURPOSE: Vitamin D has been implicated in lowering lung cancer risk, but serological data on the association among never-smoking women are limited. We report results examining the association of serum 25-hydroxyvitamin D [25(OH)D] concentrations with lung cancer risk among female never smokers. We also examined whether the association was modified by vitamin D supplementation and serum vitamin A concentrations. METHODS: In the Women's Health Initiative, including the calcium/vitamin D (CaD) Trial, we selected 298 incident cases [191 non-small cell lung cancer (NSCLC) including 170 adenocarcinoma] and 298 matched controls of never smokers. Baseline serum 25(OH)D was assayed by a chemiluminescent method. Logistic regression was used to estimate odds ratios (ORs) for quartiles and predefined clinical cutoffs of serum 25(OH)D concentrations. RESULTS: Comparing quartiles 4 versus 1 of serum 25(OH)D concentrations, ORs were 1.06 [95% confidence interval (CI) 0.61-1.84] for all lung cancer, 0.94 (95% CI 0.52-1.69) for NSCLC, and 0.91 (95% CI 0.49-1.68) for adenocarcinoma. Comparing serum 25(OH)D ≥ 75 (high) versus <30 nmol/L (deficient), ORs were 0.76 (95% CI 0.31-1.84) for all lung cancer, 0.71 (95% CI 0.27-1.86) for NSCLC, and 0.81 (95% CI 0.31-2.14) for adenocarcinoma. There is suggestive evidence that CaD supplementation (1 g calcium + 400 IU D3/day) and a high level of circulating vitamin A may modify the associations of 25(OH)D with lung cancer overall and subtypes (p interaction <0.10). CONCLUSIONS: In this group of never-smoking postmenopausal women, the results did not support the hypothesis of an association between serum 25(OH)D and lung cancer risk.

"Finding the needle in a haystack": oncologic evaluation of patients treated for LUTS with holmium laser enucleation of the prostate (HoLEP) versus transurethral resection of the prostate (TURP).

PURPOSE: To evaluate oncologic parameters of men with bothersome LUTS undergoing surgical treatment with HoLEP or TURP. METHODS: Five hundred and eighteen patients undergoing HoLEP (n = 289) or TURP (n = 229) were retrospectively analyzed for total PSA, prostate volume, PSA density, history of prostate biopsy, resected prostate weight, and histopathological features. Univariate and multivariate logistic regression models were used to identify independent predictors of incidental PCa (iPCa). RESULTS: Men undergoing HoLEP had a significantly higher total PSA (median 5.5 vs. 2.3 ng/mL) and prostate volume (median 80 vs. 41 cc), and displayed a greater reduction of prostate volume after surgery compared to TURP patients (median 71 vs. 50%; all p < 0.001). With a prevalence of incidental PCa (iPCa) of 15 and 17% for HoLEP and TURP, respectively, the choice of procedure had no influence on the detection of iPCa (p = 0.593). However, a higher rate of false-negative preoperative prostate biopsies was noted among iPCa patients in the HoLEP arm (40 vs. 8%, p = 0.007). In multivariate logistic regression, we identified patient age (OR 1.04; 95% CI 1.01-1.07, p = 0.013) and PSA density (OR 2.13; 95% CI 1.09-4.18, p = 0.028) as independent predictors for the detection of iPCa. CONCLUSIONS: Despite differences in oncologic parameters, the choice of technique had no influence on the detection of iPCa. Increased patient age and higher PSA density were associated with iPCa. A higher rate of false-negative preoperative prostate biopsies was noted in HoLEP patients. Therefore, diagnostic assessment of LUTS patients requires a more adapted approach to exclude malignancy, especially in those with larger prostates.

Neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios predict chemotherapy outcomes and prognosis in patients with colorectal cancer and synchronous liver metastasis.

BACKGROUND: Recent evidence indicates that inflammatory parameters could be useful to predict metastasis from colorectal cancer. However, their roles in predicting chemotherapy response and prognosis in patients with synchronous colorectal liver metastasis (CLM) are unknown. METHODS: The clinical data and baseline laboratory parameters of 55 patients with synchronous CLM were retrospectively reviewed. All patients underwent palliative resection of the primary tumor and oxaliplatin-based chemotherapy. Two indices of systemic inflammation were reviewed-neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR)-preoperatively and before the second cycle of chemotherapy. Associations between prognostic variables and tumor response, progression, and survival were investigated. RESULTS: NLR < 4 and PLR < 150 were correlated with better disease control (p = 0.024 and 0.026, respectively). In univariate analysis, elevated NLR and PLR were significant prognostic factors for poor overall survival (OS) and progression-free survival (PFS). In multivariate analysis, PLR (p = 0.027), age (p = 0.018), resection of liver metastases (p = 0.017), and lactate dehydrogenase level (p = 0.011) were independent predictors of PFS, while resection of liver metastases was the only independent predictor of OS (p = 0.002). In addition, when patients were divided into groups according to changes in NLR and/or PLR, reduced NLR and PLR were associated with improved disease control (p = 0.038 and 0.025, respectively). Normalization of NLR also was associated with improved PFS. CONCLUSIONS: NLR and PLR are potentially useful clinical biomarkers to predict chemotherapy response in patients with synchronous CLM. PLR also may be useful to predict PFS in these patients.

Cranberry intervention in patients with prostate cancer prior to radical prostatectomy. Clinical, pathological and laboratory findings.

BACKGROUND AND OBJECTIVES: Recently, we described an inverse association between cranberry supplementation and serum prostate specific antigen (PSA) in patients with negative biopsy for prostate cancer (PCa) and chronic nonbacterial prostatitis. This double blind placebo controlled study evaluates the effects of cranberry consumption on PSA values and other markers in men with PCa before radical prostatectomy. METHODS: Prior to surgery, 64 patients with prostate cancer were randomized to a cranberry or placebo group. The cranberry group (n=32) received a mean 30 days of 1500 mg cranberry fruit powder. The control group (n=32) took a similar amount of placebo. Selected blood/urine markers as well as free and total phenolics in urine were measured at baseline and on the day of surgery in both groups. Prostate tissue markers were evaluated after surgery. RESULTS: The serum PSA significantly decreased by 22.5% in the cranberry arm (n=31, P<0.05). A trend to down-regulation of urinary beta-microseminoprotein (MSMB) and serum gamma-glutamyltranspeptidase, as well as upregulation of IGF-1 was found after cranberry supplementation. There were no changes in prostate tissue markers or, composition and concentration of phenolics in urine. CONCLUSIONS: Daily consumption of a powdered cranberry fruit lowered serum PSA in patients with prostate cancer. The whole fruit contains constituents that may regulate the expression of androgen-responsive genes.