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.

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.

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.

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.

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.

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.

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.

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.

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.

[Radiation therapy in simultaneous choroidal and brain metastases]. / La radioterapia en el tratamiento de las metástasis coroideas y cerebrales simultáneas.

Choroidal metastases from lung cancer can be the initial clinical manifestation of metastasic disease, although they generally coexist with at least two more metastasic sites. The most common symptom is decreased vision, however 20% of brain metastases can present with visual alterations. A differential diagnosis within brain metastases and/or choroidal is necessary. We present the case of a patient with lung cancer and decreased vision who was diagnosed as simultaneous choroidal and brain metastases. Radiation therapy (20Gy/5fractions) significantly improves decreased vision. This case shows that, although life expectancy of patients with metastasic lung cancer is short, an adequate diagnosis and treatment, can improve the quality of life of those patients.

Can Karnofsky performance status be transformed to the Eastern Cooperative Oncology Group scoring scale and vice versa?

There is no consensus regarding the equivalence of performance status between the Karnofsky (KPS) and the Eastern Cooperative Oncology Group (ECOG) scales. In the present study KPS and ECOG scores were compared in 150 consecutive cancer patients. An empirical relation was established through regression analysis in a subsample of 75 patients and the results tested in the second subsample. Transformation tables including 95 and 66% confidence intervals were calculated. Both performance scales are highly correlated, but inferences about individual patients were subject to a high level of error. These results stress the difficulty of translating one score to another, especially in the range of lower performance status where a wide spread is observed.

Influence of dose-rate on inflammatory damage and adhesion molecule expression after abdominal radiation in the rat.

PURPOSE: The goal of this study was to assess the effects of two clinically relevant radiation dose-rates on endothelial adhesion molecule expression, inflammatory response, and microvascular dysfunction. METHODS AND MATERIALS: Rats were irradiated with 10 Gy at low (0.9 Gy/min) or high (3 Gy/min) dose-rates. Control animals received sham irradiation. Leukocyte rolling, adhesion, emigration, and microvascular permeability were assessed in mesenteric venules by intravital microscopy 6 hours after irradiation. P-selectin and intercellular adhesion molecule-1 (ICAM-1) expression were measured using radiolabeled monoclonal antibodies. RESULTS: Low dose-rate (LDR) abdominal irradiation increased leukocyte adhesion compared with sham-irradiated animals, whereas high dose-rate (HDR) irradiation resulted in enhanced leukocyte rolling, adhesion, and emigration, compared with the LDR or with sham-irradiated rats. Both dose-rates increased microvascular permeability, although this effect was significantly greater after radiation with the high (8-fold) than the low (5-fold) dose-rate. HDR radiation induced significantly larger increments in P-selectin expression in splanchnic organs than LDR, whereas in most organs ICAM-1 expression was only upregulated by the HDR. Blockade of ICAM-1, but not P-selectin, abrogated leukocyte adhesion at both dose-rates. CONCLUSIONS: The magnitude of upregulation of endothelial adhesion molecules, leukocyte recruitment, and endothelial barrier dysfunction elicited by radiation therapy is dependent on the dose-rate at which the radiation is delivered.

Effects of single dose irradiation on pancreatic beta-cell function.

We have irradiated abdominal cavity of 23 rats with 10 Gy irradiation-induced hypoglycemia on the fourth day after intervention. Islets collected at this time showed an impaired insulin secretion without affecting insulin content. This impairment persisted after one month follow-up with reduced number of beta-cells in morphological examination.

Tepoxalin inhibits inflammation and microvascular dysfunction induced by abdominal irradiation in rats.

BACKGROUND: Inflammatory cells contribute to the acute and sub-acute sequelae of radiation therapy. Tepoxalin, an inhibitor of cyclooxygenase and 5-lipoxygenase that suppresses NF-kappaB activation, has potent anti-inflammatory activity. AIMS: To assess the effects of tepoxalin on radiation-induced inflammatory damage, and determine its mechanisms of action. METHODS: Leucocyte rolling, adhesion and emigration, and albumin leakage were determined by intra-vital microscopy in rat mesenteric venules. NF-kappaB activation was measured by electrophoretic mobility shift assays, and endothelial intercellular adhesion molecule-1 expression by the radiolabelled antibody technique. Groups of irradiated rats were treated with tepoxalin, N-acetyl-L-cysteine, zileuton (lipoxygenase inhibitor), or vehicle. RESULTS: Irradiated animals had a marked increase in the number of rolling, adherent and emigrated leucocytes in mesenteric venules, and in microvascular permeability. Tepoxalin prevented leucocyte adhesion and the increase in permeability after radiation. Tepoxalin did not inhibit radiation-induced NF-kappaB activation or intercellular adhesion molecule-1 up-regulation, while N-acetyl-L-cysteine, which attenuated NF-kappaB activation, had no effect on leucocyte recruitment. In contrast, tepoxalin inhibited the increase in leukotriene B4 levels after radiation, and the anti-inflammatory effects of the drug were mimicked by zileuton. CONCLUSIONS: Tepoxalin affords significant protection against radiation-induced inflammation and microvascular dysfunction in splanchnic organs through a mechanism dependent on leukotriene synthesis inhibition.

Role of postoperative radiation therapy in stage IIIa non-small cell lung cancer.

One hundred forty-six patients with pathological stage IIIa non-small cell lung cancer were retrospectively analyzed to determine whether postoperative radiation therapy improves survival and reduces locoregional recurrences. The survival rate of the overall group at 1, 3, and 5 years was 56%, 24%, and 17%, respectively. Regarding the type of resection and histology, we did not observe statistically significant differences. Patients with N0 and N1 disease were grouped and compared with the N2 group, and survival at 3 and 5 years was 41% and 27%, respectively, for the T3 N0-1 group and 17% and 15%, respectively, for the T3 N2 group (p less than 0.001 and p = 0.05, respectively). Eighty-six patients received postoperative irradiation (45 to 50 Gy) and 60 did not. We have not observed any improvement in survival with postoperative radiation therapy, except in those patients with N2 disease. Median survival time was 6 months for patients without irradiation and 15 months for those with irradiation (p = 0.071). According to locoregional recurrences, a slight benefit with postoperative radiation therapy was observed.

Symptom prevalence in the last week of life.

Palliative care is the management of patients with progressive, far-advanced disease for whom the prognosis is limited and the focus of care is quality of life. During the last days of life, it is important to redefine the goals, as previously present symptoms may increase and new symptoms may appear. To assess these symptoms, 176 patients were evaluated. A questionnaire evaluated symptoms during the last week of life and compared these prevalences with those at the first evaluation. The patients comprised 121 men and 55 women. The mean age was 67.7 years. Metastases were present in 66.5% and were multiple in 52%. The most frequent symptoms at the end of life (> 50%) were anorexia, asthenia, dry mouth, confusion, and constipation. The majority of patients died at home (64.2%). We observed good control of "reversible" symptoms, but many symptoms were difficult to control at the end of life. Symptom assessment is important in this population.

Usefulness of strontium-89 for bone pain palliation in metastatic breast cancer patients.

Most studies of prostate cancer have shown that strontium-89 chloride (89Sr) is effective in the palliation of metastatic bone pain, refractory to conventional analgesia. The aim of this study was to evaluate the usefulness of 89Sr for bone pain palliation in breast cancer patients. Forty women were treated with 148 MBq of 89Sr. Six patients were retreated, receiving two or more doses. The Karnofsky performance status was assessed and pain and analgesia were scored on scales of 9 and 5 points, respectively. The efficacy of 89Sr was evaluated at 3 months of treatment. The response was good in 60% of the patients and partial in 32%; there was no response in the remaining 8% (pre-treatment Karnofsky < or = 60). The duration of the response was 120+/-143 days. In the patients retreated, the response was good in 83% and partial in 17%, without significant differences compared with the first dose, but the pre-treatment Karnofsky and the duration of the efficacy were lower (P < 0.05). A transient and slight decrease of leukocyte and platelet counts after the first month of treatment with 59Sr was observed. In conclusion, breast cancer patients with metastatic bone pain can benefit from therapy with 89Sr. If necessary, the treatment may be repeated safely and with the same efficacy as is achieved after the first dose. A low functional performance status could be a cause of the lower effectiveness of 89Sr.

Radiotherapy for in situ extramammary Paget disease of the vulva.

BACKGROUND: Radiotherapy as a first-choice treatment for in situ extramammary Paget disease has been successfully used. OBJECTIVES: To review the most relevant aspects of radiotherapy as first-choice treatment in selected cases of in situ extramammary Paget disease of the vulva. PATIENTS AND METHODS: Two Caucasian females aged 76 and 92 years with in situ extramammary Paget disease localized in the genital region were treated by means of ortovoltage X-rays: 100 kV, 8 mA, 1.7 mm Al filter, field size of 12-cm cone, and source skin distance of 30 cm. Both patients received 40 Gy, 200 cGy per fraction, five fractions per week. RESULTS: Complete regression of in situ extramammary Paget disease was observed in both patients after radical radiation therapy and neither local recurrences nor internal malignancies were detected. CONCLUSIONS: Radiotherapy is a curative treatment in selected cases of in situ extramammary Paget disease affecting the vulva.

Effects of injection position and transponder size on the performances of passive injectable transponders used for the electronic identification of cattle.

A total of 686 Tiris half-duplex passive injectable transponders (PIT) of two sizes (23 and 32 mm) were randomly injected s.c. in three positions, armpit, ear scutulum, and upper lip, in 343 fattening calves (1 to 3 mo old). Injections were performed by two trained and two untrained operators. Losses and breakages on the farm were recorded at wk 1, 3, 7, 11, and 15 in restrained animals using two types of hand-held transceivers with a stick antenna. Dynamic reading efficiency (DRE) in animals running through a raceway was also evaluated at wk 1 and 3 and monthly until slaughter, using a stationary transceiver working at 137 dB x microV x m(-1) at 3 m. The total number of PIT that fell or broke in the slaughtering line, the location method, and the recovery time were also recorded. Results on the farm showed low breakages on average (0.4%) and differences (P < 0.05) in losses according to position (armpit, 1.7%; ear, 5.2%; and lip, 14.0%). An interaction (P < 0.05) between position x size was observed, and losses were greatest using a 32-mm PIT in the lip. The DRE was affected (P < 0.05) by PIT position and size, and values were greater for the 32-mm PIT in all positions (armpit: 99.9 +/- 0.1 vs 95.8 +/- 4.9%; ear: 93.8 +/- 2.2 vs 81.9 +/- 4.6%; lip: 66.8 +/- 4.9 vs 53.4 +/- 4.7%, respectively, for 32 vs 23 mm). Recovery of PIT in the abattoir was on average 96.7, 96.7, and 99.2% for armpit, ear, and lip, respectively (P > 0.05). Most of the PIT injected in the armpit were recovered by sight or palpation, but 31.9% were recovered after cutting the muscles around the area and 10.7% were recovered on the internal side of the hide, which jeopardized carcass identification. Recovery of PIT injected in the ear was 23.4% in the hide and 76.6% in the auricular muscles of the head. The easiest recovery was in the lip, 8.9% of PIT were located in the hide and 91.1% in the head. Recovery time was affected (P < 0.05) by position: the quickest was lip (27 +/- 2 s), followed by ear (52 +/- 5 s) and armpit (78 +/- 7 s). In conclusion, taking into account retention and reading performances, injection of a 32-mm PIT into the armpit showed the best results on the farm, but a careful and longer recovery was needed in the abattoir. Improvement of recovery methodology and time would be necessary in order to recommend injection of PIT in the armpit instead of in the ear for cattle tracking or monitoring.