Unveiling the mechanisms of immune evasion in pancreatic cancer: may it be a systemic inflammation responsible for dismal survival?

PURPOSE: Pancreatic cancer (PC) is one of the most aggressive malignancies with no effective treatment if diagnosed in advanced stage. Systemic inflammation is a recognized characteristic of cancer progression, and we believe that the understanding of the influence of inflammatory parameters may contribute to therapeutic improvement in PC. Here, we validated the Eosinophil/Lymphocyte Ratio (ELR) together with the Neutrophil/Lymphocyte Ratio (NLR) and their components, as prognostic factors in PC patients treated with chemoradiation. METHODS: A total of 66 consecutive patients (p) diagnosed with PC stage I-III and treated with External Beam Radiotherapy + chemotherapy ± surgery (28p) in our institution from 2007 to 2018 were retrospectively evaluated. The impact of pre-treatment ELR ≥ 0.04, NLR ≥ 1.9, neutrophilia (≥ 7.0 × 10(9)/l), eosinophilia (≥ 0.5 × 10(9)/l) and lymphopenia (< 1.0 × 10(9)/l) on Overall Survival (OS) and Time-to-Progression (TTP) was evaluated both in the entire cohort and separately according to surgical status. RESULTS: Higher ELR was associated with longer OS and TTP, both in surgically treated and not operable patients. On univariate analysis, elevated ELR was associated with better OS (HR = 0.3, 95% IC 0.13-0.65, p = 0.003), contrarily to neutrophilia (HR = 2.7, 95% IC 1.2-6.5, p = 0.026) and age > 50 years (HR = 2.6, 95% IC 1.03-6.6, p = 0.044), while NLR, lymphopenia and Ca-19.9 were not significant. On multivariate regression, independent prognosticators for OS were: ELR, age and neutrophilia; while for TTP: ELR, neutrophilia, eosinophilia and lymphopenia. CONCLUSIONS: The host's immune response influences survival outcomes of PC patients and may be of interest for future research.

Phase II trial of preoperative chemoradiotherapy with oxaliplatin, cisplatin, and 5-FU in locally advanced esophageal and gastric cancer.

BACKGROUND: Based on a phase I study showing the feasibility of combining of oxaliplatin, cisplatin, and 5-fluorouracil (5-FU) (OCF) with radiation therapy (RT) in esophageal cancer, the efficacy of this regimen in esophageal, gastroesophageal (GE), and gastric (G) cancer was assessed in this phase II multicenter study. PATIENTS AND METHODS: Patients with resectable tumors were eligible. Treatment included two cycles of oxaliplatin 85 mg/m(2), cisplatin 55 mg/m(2), and continuously infused 5-FU 3 g/m(2) in 96 h and concurrent RT (45 Gy), followed by surgery after 6-8 weeks. Primary end point was complete pathologic response (pCR). RESULTS: Forty-one patients were enrolled. Tumor location was esophagus 39% (squamous 10/adenocarcinoma 6), GE junction 32%, and stomach 29%. G3-G4 adverse events included asthenia (27%) and neutropenia (14%). One toxic death occurred. Thirty-one patients (75.6%) underwent surgery (R0 in 94%). Pathologic response was achieved in 58% of patients, with pCR in 50% and 16% of esophageal and GE/G cancer, respectively. pCR was achieved in 67% of squamous cell carcinoma. Survival: median follow-up, 50.4 months; median progression-free survival and overall survival were 23.2 and 28.4 months, respectively. CONCLUSION: Preoperative OCF plus RT showed an acceptable toxicity and promising activity especially in squamous cell esophageal cancer.

Comparison of positron emission tomography (PET) and computed tomography (CT) for better target volume definition in radiation therapy planning

BACKGROUND: In cancer patients, positron emission tomography/ computed tomography (PET/CT) fused images present less variability in target contouring, respect to use only CT images, respectively. However, the gold standard has not yet been clearly established between radiation oncologists with regard to PET images and the methodology of contouring targets with confidence using PET/CT fused images. The aim of this study was to determine whether integrated PET/CT fused images provide advantages in virtual simulation compared with morphological contouring only with CT. MATERIAL AND METHODS: Thirty cancer patients were evaluated in an adapted PET/CT hybrid in radiotherapy (RT) setup position, with 20 of them being suitable for RT: 17 were suitable for curative intent, which was the group of interest in this study. All image series were sent to the RT work station (WS) where CT and PET series were automatically fused by Digital Imaging and Communications in Medicine (DICOM) in each case. PET series were threshold and were subjected to source-to-background contrast algorithms to fi nally redefine the original tumour description. Three different radiotherapy plans (RTP) for each patient were compared after targets were contoured: [1] planning over metabolic (PET) contoured targets, [2] planning over only morphologic (CT) targets, and [3] planning over targets obtained for treatment based on fused PET/CT images. RESULTS: PET/CT findings altered initial-stage planning in four patients (23.5%) because they had been undergoing chemotherapy. Gross target volume (GTV) and planning target volume (PTV) based only on PET showed more homogeneity to obtain mean doses (p = 0.025) with respect to those based on PET/CT, respectively. However, no percentage differences were observed in median PTV doses between the planning methods, although there was higher variability in PET/CT planning. Morphological (CT) and PET/ CT target volumes were more voluminous than metabolic (PET) volumes. On the other hand, 20% of metabolic (PET) PTV were out of those defined by PET/CT. Thoracic RT plans based on PET preserved better bilateral lung [percentage volume of lung irradiated with a dose of 20 Gy (V20); significance, R(2) = 0.559, p = 0.006]. CONCLUSIONS: For our physicians, PET/CT fused images allowed better contouring of primary tumours in 40% of head and neck cancers and 34% of thoracic cancers. PET/CT provides useful information for virtual simulation therapy. Image treatment and planning in an RT workstation is mandatory (AU)

Loco-regional control after postoperative radiotherapy for patients with regional nodal metastases from melanoma

INTRODUCTION: The role of adjuvant radiation therapy (RT) following nodal surgery in malignant melanoma remains controversial. There are no published randomised trials comparing surgery alone to surgery with postoperative RT. AIM AND METHODS: The purpose of the present retrospective study was to review the results of loco-regional control after postoperative RT in patients with nodal metastases of melanoma. Seventy-seven patients with high-risk disease (lymph nodes > or =3 cm, more than three lymph nodes involved, extracapsular extension and recurrent disease) were treated with adjuvant RT. Hypofractionation was used in 65 patients and conventional fractionation in 12 patients. RESULTS: Seventy-seven patients with nodal metastases from melanoma were managed with lymphadenectomy and radiation, with or without systemic therapy. The median age was 56 years old (range: 21-83). There were 47 males (61%) and 30 females (39%). Loco-regional control was observed in 95% of patients (73/77). The actuarial 5-year in-field loco-regional control rate was 90% (mean: 105 months; CI95%: 96-115 months). Median metastasis disease- free survival (MDFS) was 16 months (CI95%: 13-18 months). Median survival time (MST) for the entire group was 26 months (CI95%: 18-34 months). MST according to the localisation of node metastases (groin, axilla and cervical) was also analysed, without statistically significant differences (p=0.08). Concerning the number of risk factors score, analysis of survival did not show statistically significant differences (p=0.055). CONCLUSIONS: Despite the high incidence of distant metastases, loco-regional control remains an important goal in the management of melanoma. Surgery and adjuvant RT provides excellent loco-regional control, although distant metastases remain the major cause of mortality (AU)

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Prognostic value of tyrosinase reverse transcriptase PCR analysis in melanoma sentinel lymph nodes: long-term follow-up analysis.

OBJECTIVE: To determine the prognostic value of detecting tyrosinase transcripts in melanoma sentinel lymph nodes (SLNs). METHODS: Reverse transcription (RT) PCR for tyrosinase mRNA was performed on negative SLNs of 76 patients with melanoma. RESULTS: Tyrosinase mRNA was found in 39 patients (51.3%). After a median follow-up period of 51 months, significant differences were found in overall survival (OS) but not in disease-free survival (DFS). The 5-year OS and DFS rates were 97.2% and 80%, respectively, for RT-PCR tyrosinase-negative (TN) patients vs. 78.67% and 66.24% for RT-PCR tyrosinase-positive (TP) patients (P = 0.019 and P = 0.38, respectively). Of four progressing patients in the TN group, three relapsed with subcutaneous, soft-tissue or lymph-node metastases, while seven out of nine progressing patients in the TP group relapsed at visceral sites. CONCLUSIONS: No significant differences in DFS were found by RT-PCR tyrosinase expression analysis at melanoma SLNs. Significant differences in OS could be related to a different pattern of relapse and must be confirmed after a longer follow-up time.

Metastasis to the nasal cavity from primary rectal adenocarcinoma.

We describe a rare case of metastasis to the pa ra - na sal sinuses. The lesion had an immunohistochemical (positivity for cytokeratin 20, negativity for cytokeratin 7, overexpression of p53) and in situ hybridisation profile (neither lesions showed deletion for p53) consistent with metastasis from the earlier rectal adenocarcinoma. The correct typification of intestinal-type neoplasms requires a combination of morphological, immunohistochemical and, sometimes, molecular analysis.

Metastasis to the nasal cavity from primary rectal adenocarcinoma

We describe a rare case of metastasis to the pa ra - na sal sinuses. The lesion had an immunohistochemical (positivity for cytokeratin 20, negativity for cytokeratin 7, overexpression of p53) and in situ hybridisation profile (neither lesions showed deletion for p53) consistent with metastasis from the earlier rectal adenocarcinoma. The correct typification of intestinal-type neoplasms requires a combination of morphological, immunohistochemical and, sometimes, molecular analysis (AU)

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Brain nodules with lung mass: are they always metastases?

In a smoking adult with a lung mass, brain masses are usually diagnosed as brain metastases of lung origin. Nevertheless, differential diagnosis between cerebral abscesses cannot be performed based on clinical symptoms or imaging technologies, and histological diagnosis is essential. This case illustrates the advisability of always obtaining histological diagnosis of the primary tumor and/or cerebral lesion before introducing any oncological treatment (AU)

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Occipital condyle syndrome secondary to bone metastases from rectal cancer.

Skull-base metastases are very unfrequent. Occipital condyle syndrome (OCS) is usually underdiagnosed. Until now few cases have been reported in the literature. We present a 71-year-old woman with metastatic rectum adenocarcinoma, with right occipital headache and ipsilateral hypoglossal palsy, diagnosed by computed tomography and magnetic resonance imaging of OCS due to a skull-base metastasis and treated with radiation therapy.

Occipital condyle syndrome secondary to bone metastases from rectal cancer

Skull-base metastases are very unfrequent. Occipital condyle syndrome (OCS) is usually underdiagnosed. Until now few cases have been reported in the literature. We present a 71-year-old woman with metastatic rectum adenocarcinoma, with right occipital headache and ipsilateral hypoglossal palsy, diagnosed by computed tomography and magnetic resonance imaging of OCS due to a skull-base metastasis and treated with radiation therapy (AU)

Incidence of radiation-induced leukoencephalopathy after whole brain radiotherapy in patients with brain metastases.

INTRODUCTION: Whole brain radiation therapy (WBRT) remains a recommended treatment for patients with brain metastases in terms of symptom palliation, especially when extracranial systemic disease is present. The aim of the study was to determine the clinical correlation between pre-existing leukoaraiosis and posterior leukoencephalopathy secondary to WBRT. METHODS AND MATERIALS: We retrospectively reviewed the results of WBRT treatment in 44 patients with melanoma brain metastases. The neuroimaging abnormalities of the white matter (T2-weighted MRI) were graded over time. RESULTS: From the 37 evaluable patients the mean age was 53 years old, 23 male and 14 female. Vascular risk factors were present in 22 patients (59.5%). The WBRT total dose was 20 Gy/5fr (n=21) and 30 Gy/10fr (n=16). Leukoaraiosis pre-WBRT was observed in 9/37 patients (24.3%) and leukoencephalopathy post-WBRT in 2/37 (5.4%). Univariate analysis of prognostic factors (sex, age and vascular risk factors) for leukoaraiosis was conducted observing statistically significant differences for patients with age>or=65 years old (p=0.003). Nineteen patients survived more than 3 months. Twelve patients (63.2%) suffered from vascular risk factors. Univariate analysis demonstrated previous leukoaraiosis as a prognostic factor for developing further leukoencephalopathy after WBRT (p=0.015). CONCLUSIONS: Radiation-induced leukoencephalopathy is greater in patients with pre-existing leukoaraiosis. Because of the potential of long-term survival in a small subset of patients with brain metastases and the risk of radiation-induced dementia, neurotoxicity reduction in patients with leukoaraiosis is an important goal of treatment.

Incidence of radiation-induced leukoencephalopathy after whole brain radiotherapy in patients with brain metastases

INTRODUCTION: Whole brain radiation therapy (WBRT) remains a recommended treatment for patients with brain metastases in terms of symptom palliation, especially when extracranial systemic disease is present. The aim of the study was to determine the clinical correlation between pre-existing leukoaraiosis and posterior leukoencephalopathy secondary to WBRT. METHODS AND MATERIALS: We retrospectively reviewed the results of WBRT treatment in 44 patients with melanoma brain metastases. The neuroimaging abnormalities of the white matter (T2-weighted MRI) were graded over time. RESULTS: From the 37 evaluable patients the mean age was 53 years old, 23 male and 14 female. Vascular risk factors were present in 22 patients (59.5%). The WBRT total dose was 20 Gy/5fr (n=21) and 30 Gy/10fr (n=16). Leukoaraiosis pre-WBRT was observed in 9/37 patients (24.3%) and leukoencephalopathy post-WBRT in 2/37 (5.4%). Univariate analysis of prognostic factors (sex, age and vascular risk factors) for leukoaraiosis was conducted observing statistically significant differences for patients with age>or=65 years old (p=0.003). Nineteen patients survived more than 3 months. Twelve patients (63.2%) suffered from vascular risk factors. Univariate analysis demonstrated previous leukoaraiosis as a prognostic factor for developing further leukoencephalopathy after WBRT (p=0.015). CONCLUSIONS: Radiation-induced leukoencephalopathy is greater in patients with pre-existing leukoaraiosis. Because of the potential of long-term survival in a small subset of patients with brain metastases and the risk of radiation-induced dementia, neurotoxicity reduction in patients with leukoaraiosis is an important goal of treatment (AU)

Pathological femur fracture secondary to radiation therapy for soft tissue sarcoma.

Bone fracture is a well known possible late complication of radiation treatment. Little has been written about fractures of long bones after irradiation. We present a case of femur bone necrosis secondary to postoperative radiation for a soft tissue sarcoma of the thigh 20 years earlier. Fixation of the diaphyseal fracture and radiological evolution are described.

Pathological femur fracture secondary to radiation therapy for soft tissue sarcoma

Bone fracture is a well known possible late complication of radiation treatment. Little has been written about fractures of long bones after irradiation. We present a case of femur bone necrosis secondary to postoperative radiation for a soft tissue sarcoma of the thigh 20 years earlier. Fixation of the diaphyseal fracture and radiological evolution are described (AU)

Clinical outcome in patients with intramedullary spinal cord metastases from lung cancer.

Intramedullary spinal cord metastases (ISCM) are uncommon and present with rapidly progressing neurological deficits. The objective of this study was to determine the rate, duration of neurological response and survival after radiation therapy. We have retrospectively reviewed the clinical outcome of six cases with a diagnosis of ISCM from primary lung cancer, non-small cell (NSCLC) (n=3) and small cell (SCLC) (n=3). Total radiation dose ranged from 27 Gy/5 fr to 40 Gy/20 fr. Ambulation was preserved in 3 patients and partially recovered in one. Five out of the six patients (83%) showed improvement in neurological signs/symptoms with a mean duration of 17.2 days (max: 40 days; min: 6 days). Median survival time was 5 months (confidence interval (CI) 95%: 0-12) for NSCLC and 5 months (CI 95%: 4-6) for SCLC. Although radiation response rate is high, the interval free of neurological progression is very short. A therapeutic approach should be considered for each individual.

Low dose rate brachytherapy in lip carcinoma.

BACKGROUND: Lip cancer is frequently treated with surgery although radiation therapy offers comparable results. The aim of the study was to evaluate the local cure rate in patients with lip carcinoma treated with 192-Ir low dose rate interstitial brachytherapy. METHODS: Fifty-four patients with a mean age of 70 years (range, 40-90 years) were retrospectively evaluated. The tumour location was the superior lip in 4 (7.4%) and the inferior lip in 50 (92.6%). Tumour stage was T1N0 in 33 patients and T2N0 in 21 patients. The radioactive sources with hypodermic needles in 49 patients (90.7%) and plastic tubes in 5 (9.3%) were placed parallel and equidistant from one another across the tumour volume according to the Paris system rules. RESULTS: The median dose was 61.5 Gy (range, 60-65 Gy). All patients experienced acute brisk skin and mucositis RTOG grade III around the implanted volume, subsiding within 4-6 weeks after the implant. Local control was achieved in 98% of patients. The mean follow-up was 7 years. CONCLUSIONS: Low dose rate interstitial brachytherapy with 192-Iridium is a well established and efficacious way to achieve local control of the tumour in lip cancer. It offers the advantage of avoiding surgery in an elderly population.

Low dose rate brachytherapy in lip carcinoma

BACKGROUND: Lip cancer is frequently treated with surgery although radiation therapy offers comparable results. The aim of the study was to evaluate the local cure rate in patients with lip carcinoma treated with 192-Ir low dose rate interstitial brachytherapy. METHODS: Fifty-four patients with a mean age of 70 years (range, 40-90 years) were retrospectively evaluated. The tumour location was the superior lip in 4 (7.4%) and the inferior lip in 50 (92.6%). Tumour stage was T1N0 in 33 patients and T2N0 in 21 patients. The radioactive sources with hypodermic needles in 49 patients (90.7%) and plastic tubes in 5 (9.3%) were placed parallel and equidistant from one another across the tumour volume according to the Paris system rules. RESULTS: The median dose was 61.5 Gy (range, 60-65 Gy). All patients experienced acute brisk skin and mucositis RTOG grade III around the implanted volume, subsiding within 4-6 weeks after the implant. Local control was achieved in 98% of patients. The mean follow-up was 7 years. CONCLUSIONS: Low dose rate interstitial brachytherapy with 192-Iridium is a well established and efficacious way to achieve local control of the tumour in lip cancer. It offers the advantage of avoiding surgery in an elderly population (AU)

Melanoma inhibiting activity protein (MIA), beta-2 microglobulin and lactate dehydrogenase (LDH) in metastatic melanoma.

BACKGROUND: Serum levels of melanoma markers may have a role in monitoring disease evolution in metastatic melanoma. PATIENTS AND METHODS: Serial measurements of melanoma inhibiting activity protein (MIA), lactate dehydrogenase (LDH), S-100 and beta2-microglubulin were obtained from 42 metastatic melanoma patients during their biochemotherapy treatment. RESULTS: High pre-treatment serum levels of S-100, LDH, MIA and P2-microglobulin were detected in 50%, 57%, 50% and 24% of the patients, respectively. Only S-100 had prognostic significance for both disease-free (p=0.011) and overall survival (p=0.021). In patients who responded to treatment, S-100 levels decreased significantly from pre-treatment to the time of response (p = 0.050). When patients progressed, levels of MIA and P2-microglobulin increased significantly (p =0.028 and p =0.030, respectively). CONCLUSION: Correlation with disease evolution was found for S-100, MIA and P2-microglobulin levels. Despite the small sample size of the study, S-100 was a significant prognostic marker for overall survival and disease-free survival.

Clinical outcome in patients with intramedullary spinal cord metastases from lung cancer

Intramedullary spinal cord metastases (ISCM) are uncommon and present with rapidly progressing neurological deficits. The objective of this study was to determine the rate, duration of neurological response and survival after radiation therapy. We have retrospectively reviewed the clinical outcome of six cases with a diagnosis of ISCM from primary lung cancer, non-small cell (NSCLC) (n=3) and small cell (SCLC) (n=3). Total radiation dose ranged from 27 Gy/5 fr to 40 Gy/20 fr. Ambulation was preserved in 3 patients and partially recovered in one. Five out of the six patients (83%) showed improvement in neurological signs/symptoms with a mean duration of 17.2 days (max: 40 days; min: 6 days). Median survival time was 5 months (confidence interval (CI) 95%: 0-12) for NSCLC and 5 months (CI 95%: 4-6) for SCLC. Although radiation response rate is high, the interval free of neurological progression is very short. A therapeutic approach should be considered for each individual (AU)