Unrecognized digestive toxicities of radiation therapy.

The aim of this article is to review unrecognized toxicities resulting from radiation therapy of digestive neoplasms. Due to their precocious occurrence, acute toxicities are well-known by radiation oncologist, and their treatment well-established. Thus, acute toxicities will not be described in this review. We will focus on incidence, diagnosis, and management of late and uncommon toxicities occurring in the digestive tract and digestive organs. Prevention, by respecting healthy tissues constraints, is the main tool to reduce incidence of those rare complications. Nonetheless, once installed, late toxicities remain a major burden in terms of quality of life and can even be life threatening. Hence, information and education about their diagnosis and management is important.

Targeted Therapies in the Management of Well-Differentiated Digestive and Lung Neuroendocrine Neoplasms.

OPINION STATEMENT: Ongoing advances in our understanding of neuroendocrine tumor (NET) biology, genetics, and immunology, will continue to expand the availability of targeted therapies, thus improving the outcomes of patients. Well-differentiated neuroendocrine tumors (NETs) are grouped into pancreatic and non-pancreatic NETs (includes GI and thoracic NETs) for treatment considerations (Fig. 1). For panNETs, initial therapy is driven by the need of radiographic response, and targeted agents are typically reserved for second and third line based on the toxicity profile. Treatment options for non-pancreatic NETs are also expanding and while SSAs are the typical first-line option, everolimus and PRRT both remain approved therapies for future lines, and VEGF TKIs are showing promising results in research settings. Sequencing these agents and best time to incorporate peptide receptor radio therapy into the management algorithm remains an unmet need.

Tumor Seeding along the Puncture Tract in CT-Guided Interstitial High-Dose-Rate Brachytherapy.

PURPOSE: To quantify the occurrence of tumor seeding in computed tomography (CT)-guided high-dose-rate brachytherapy (HDRBT) and to identify potential risk factors. MATERIALS AND METHODS: CT-HDRBT is a minimally invasive therapeutic option for local ablation of unresectable tumors. The procedure involves CT-guided placement of an enclosed catheter and high-dose-rate brachytherapy using iridium-192. Transcutaneous puncture of a tumor with subsequent retraction of the applicator has the potential risk of tumor seeding along the puncture tract. A total of 1,765 consecutive CT-HDRBT procedures were performed at this center between 2006 and 2017 and were retrospectively analyzed. In addition, a distinction was made between whether the puncture tract was irradiated or not. Follow-up imaging datasets were evaluated for tumor seeding along the former puncture tracts. Descriptive and exploratory statistical analyses of the data were performed. RESULTS: Tumor seeding was observed in 25 cases (25 of 1,765 cases [1.5%]). A total of 0.008 cases occurred per person-age. Patient age was identified as a potential risk factor with an odds ratio of 1.046 (95% confidence interval, 1.003-1.091; P = .04). There were no differences between whether the puncture tract was irradiated or not (P = .552). CONCLUSIONS: Tumor seeding along the puncture tract can occur in CT-HDRBT but is rare.

Peritoneal Carcinomatosis in Gastro-Entero-Pancreatic Neuroendocrine Neoplasms: Clinical Impact and Effectiveness of the Available Therapeutic Options.

BACKGROUND: Peritoneal carcinomatosis (PC) can affect the quality of life of patients with gastro-entero-pancreatic neuroendocrine neoplasms (GEP-NENs). Peritoneal disease control by medical therapies in these patients has been poorly investigated Objectives: To describe, in a consecutive series of GEP-NENs, the clinical impact of PC and to report the effectiveness of available treatments in PC control. METHODS: A retrospective, monocenter analysis was performed of 135 GEP-NENs (1993-2016) with at least a 12-month follow-up. Peritoneal disease progression was defined as detection of a significant increase in size or appearance of new implants by imaging. RESULTS: A total of 62.9% of cases had diffuse PC (involving at least 2 abdominal quadrants). According to WHO 2017 classification, cases were 42.3% neuroendocrine tumors NET-G1, 45.5% NET-G2, 6.5% NET-G3, 4.9% neuroendocrine carcinomas NEC-G3, and 0.8% mixed neuroendocrine-nonneuroendocrine neoplasms. Bowel obstruction occurred in 30 (22.2%) patients mainly depending on size of peritoneal implants (HR: 1.10; 95% CI: 1.02-1.20; p = 0.01). Patients with diffuse PC treated with peptide receptor radionuclide therapy (PRRT) showed peritoneal progression in 37.5% of cases, and bowel obstruction or ascites in 28.1%. Better peritoneal disease control was observed in cases receiving somatostatin analogs at first-line therapy, probably due to a less aggressive disease behavior for these patients. CONCLUSIONS: Bowel obstruction is not uncommon in GEP-NENs with PC. PRRT should be adopted with caution in GEP-NENs with diffuse PC, but larger series are needed to confirm these data.

Repercusión de la radioterapia sobre la situación nutricional del paciente oncogeriátrico. ¿Puede el oncólogo radioterápico minimizar el impacto de la radioterapia sobre el estado nutricional del enfermo mayor? / Nutritional impact of radiotherapy in oncogeriatric patients. Can radiation oncologists minimize the radiotherapy impact on the nutritional status of the elderly patient?

El cáncer en pacientes ancianos representa un reto de salud a escala mundial debido al aumento de su incidencia y su mortalidad asociada. En nuestro país es la segunda causa de muerte en mayores de 65 años. En años venideros el problema irá en aumento, con un pronóstico de personas mayores de 65 años del 35% en el año 2050. La radioterapia supone una parte fundamental del tratamiento multidisciplinar del cáncer en los pacientes ancianos, donde unas veces se plantea como primera opción terapéutica y otras, como alternativa a la cirugía y/o la quimioterapia si estas plantean demasiado riesgo. El desarrollo tecnológico de la Oncología Radioterápica en los últimos años ha permitido optimizar los tratamientos y disminuir las toxicidades en los pacientes de edad avanzada, que suelen presentar mayor incidencia de comorbilidades. Es fundamental que los profesionales implicados en el tratamiento multidisciplinar del cáncer conozcan la posible toxicidad y su manejo en los pacientes oncogeriátricos, ya que, de lo contrario, disminuyen las probabilidades de que pacientes con indicación adecuada de este tratamiento lo reciban. En este sentido, es imprescindible el reconocimiento de aquellos pacientes que puedan sufrir desnutrición o estén en riesgo de sufrirla, para iniciar una intervención nutricional que minimice una pérdida de peso que altere o incluso haga suspender el tratamiento planificado

Cancer in elderly patients represents a global health challenge due to the increase in its incidence and its associated mortality. In our country it is the second leading cause of death in people over 65 years. In the coming years, the problem will increase, with a prognosis of people over 65 years of 35% in 2050. Radiotherapy is an essential part of the multidisciplinary treatment of cancer in elderly patients, where sometimes it is considered as the first therapeutic option and others, as an alternative to surgery and/or chemotherapy if they pose too much risk. The technological development of Radiation Oncology in recent years has allowed optimizing treatments and reducing side effects in elderly patients, who tend to have a higher incidence of comorbidities. It is essential that professionals involved in the multidisciplinary treatment of cancer know the possible toxicity and its management in oncogeriatric patients; otherwise, the percentage of patients who do not receive radiotherapy despite of an adequate indication will not decrease. In this sense, it is necessary to recognize those patients who may suffer from malnutrition or are at risk of suffering it, to initiate a nutritional intervention that minimizes weight loss that alters or even causes the suspension of the planned treatment

Measurement of body composition in cancer patients using CT planning scan at the third lumbar vertebra / Medición de la composición corporal en pacientes oncológicos mediante la TC de planificación a nivel de la tercera vértebra lumbar

Objective: the main objective was to assess body composition in terms of skeletal muscle index (SMI), myosteatosis, visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and intermuscular adipose tissue (IMAT) as an adjunct of information provided by radiotherapy CT planning scan. Material and methods: a sample of 49 patients with lung and digestive cancers underwent a CT scan for radiotherapy treatment, which included measurements at the L3 region. Images were analyzed with a radiotherapy contouring software, using different Hounsfield Unit (HU) settings. Cross-sectional areas (cm2) were automatically computed by summing tissue pixels and multiplying by pixel surface area. Low SMI (cm2/m2) and muscle density (HU) were determined according to the recently established cut-off points. Results: the prevalence of low SMI was detected in 46.94% of patients, being present in 8 women, 4 men with BMI < 25 kg/m2, and 11 men with BMI = 25 kg/m2. The average mean skeletal attenuation of total skeletal muscle area was 29.02 (± 8.66) HU, and myosteatosis was present in 13 women (81.25%) and 31 men (93.94%). Mean SAT was 131.92 (± 76.80) cm2, mean VAT was 133.19 (± 85.28) cm2, and mean IMAT was 11.29 (± 12.86) cm2. Conclusion: skeletal muscle abnormalities are frequently present in cancer patients and a low SMI may also exist even in the presence of overweight. As CT scans are an important tool at any radiation oncology department, they could also be used to offer highly sensitive and specific information about body composition, as well as to detect early malnutrition before starting radiotherapy treatment

Objetivo: evaluar la composición corporal mediante el índice de músculo esquelético (IME), el tejido adiposo visceral (TAV), el tejido adiposo subcutáneo (TAS) y el tejido adiposo intermuscular (TAIM) o la densidad muscular (DM) en pacientes oncológicos antes de iniciar el tratamiento con radioterapia mediante cortes de TAC. Materiales y métodos: se estudiaron 49 pacientes con cáncer de pulmón y del aparato digestivo sometidos a tomografía computarizada con cortes en L3 para la determinación del tratamiento con radioterapia. El tejido adiposo y muscular se cuantificó mediante distintas Unidades Hounsfield (UH) (-29 a +150 para masa muscular, -190 a -30 para TAIM/TAS y -150 a -50 para TAV). Resultados: la prevalencia de un IME bajo se detectó en el 46,94% de los pacientes, estando presente en 8 mujeres, 6 de ellas con un IMC = 25 kg/m². Según la distribución masculina, se identificaron 4 hombres con IMC < 25 kg/m² y 11 hombres con = 25 kg/m². La DM media fue de 29,02 (± 8,66) UH y la mioesteatosis estuvo presente en 13 mujeres (81,25%) y 31 hombres (93,94%). La media del TAS fue de 131,92 (± 76,80) cm², la del TAV de 133,19 (± 85,28) cm² y la del TAIM de 11,29 (± 12,86) cm². Conclusión: las anormalidades del músculo esquelético y la masa grasa son muy frecuentes en los pacientes con cáncer, pudiendo existir un bajo IME incluso en presencia de sobrepeso u obesidad. Teniendo en cuenta que la TAC es una herramienta importante en cualquier departamento de radioterapia, también podría utilizarse para ofrecer información sensible y específica sobre la composición corporal, así como para detectar la malnutrición precoz

Measurement of body composition in cancer patients using CT planning scan at the third lumbar vertebra.

INTRODUCTION: Objective: the main objective was to assess body composition in terms of skeletal muscle index (SMI), myosteatosis, visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and intermuscular adipose tissue (IMAT) as an adjunct of information provided by radiotherapy CT planning scan. Material and methods: a sample of 49 patients with lung and digestive cancers underwent a CT scan for radiotherapy treatment, which included measurements at the L3 region. Images were analyzed with a radiotherapy contouring software, using different Hounsfield Unit (HU) settings. Cross-sectional areas (cm2) were automatically computed by summing tissue pixels and multiplying by pixel surface area. Low SMI (cm2/m2) and muscle density (HU) were determined according to the recently established cut-off points. Results: the prevalence of low SMI was detected in 46.94% of patients, being present in 8 women, 4 men with BMI < 25 kg/m2, and 11 men with BMI ≥ 25 kg/m2. The average mean skeletal attenuation of total skeletal muscle area was 29.02 (± 8.66) HU, and myosteatosis was present in 13 women (81.25%) and 31 men (93.94%). Mean SAT was 131.92 (± 76.80) cm2, mean VAT was 133.19 (± 85.28) cm2, and mean IMAT was 11.29 (± 12.86) cm2. Conclusion: skeletal muscle abnormalities are frequently present in cancer patients and a low SMI may also exist even in the presence of overweight. As CT scans are an important tool at any radiation oncology department, they could also be used to offer highly sensitive and specific information about body composition, as well as to detect early malnutrition before starting radiotherapy treatment.

INTRODUCCIÓN: Objetivo: evaluar la composición corporal mediante el índice de músculo esquelético (IME), el tejido adiposo visceral (TAV), el tejido adiposo subcutáneo (TAS) y el tejido adiposo intermuscular (TAIM) o la densidad muscular (DM) en pacientes oncológicos antes de iniciar el tratamiento con radioterapia mediante cortes de TAC. Materiales y métodos: se estudiaron 49 pacientes con cáncer de pulmón y del aparato digestivo sometidos a tomografía computarizada con cortes en L3 para la determinación del tratamiento con radioterapia. El tejido adiposo y muscular se cuantificó mediante distintas Unidades Hounsfield (UH) (-29 a +150 para masa muscular, -190 a -30 para TAIM/TAS y -150 a -50 para TAV). Resultados: la prevalencia de un IME bajo se detectó en el 46,94% de los pacientes, estando presente en 8 mujeres, 6 de ellas con un IMC ≥ 25 kg/m². Según la distribución masculina, se identificaron 4 hombres con IMC < 25 kg/m² y 11 hombres con ≥ 25 kg/m². La DM media fue de 29,02 (± 8,66) UH y la mioesteatosis estuvo presente en 13 mujeres (81,25%) y 31 hombres (93,94%). La media del TAS fue de 131,92 (± 76,80) cm², la del TAV de 133,19 (± 85,28) cm² y la del TAIM de 11,29 (± 12,86) cm². Conclusión: las anormalidades del músculo esquelético y la masa grasa son muy frecuentes en los pacientes con cáncer, pudiendo existir un bajo IME incluso en presencia de sobrepeso u obesidad. Teniendo en cuenta que la TAC es una herramienta importante en cualquier departamento de radioterapia, también podría utilizarse para ofrecer información sensible y específica sobre la composición corporal, así como para detectar la malnutrición precoz.

Radiation Therapy in the Definitive Management of Oligometastatic Prostate Cancer: The Johns Hopkins Experience.

PURPOSE: The use of radiation therapy (RT) in consolidating oligometastatic prostate cancer (OPCa) is a rapidly evolving treatment paradigm. We review our institutional experience using metastasis-directed therapy in the definitive management of men with OPCa. METHODS AND MATERIALS: Patients with OPCa treated with definitive RT were included. The Kaplan-Meier method and multivariable Cox regression analysis were performed to assess biochemical progression-free survival (bPFS) and time to next intervention. Cumulative incidence functions were used to calculate rates of local failure. Toxicity was assessed using Common Terminology Criteria for Adverse Events (version 4). RESULTS: This study analyzed 156 patients with OPCa and 354 metastatic lesions with median follow-up of 24.6 months. Of 150 patients with toxicity data, 53 (35%) experienced acute grade 1 toxicity, 8 (5%) had grade 2, and none had grade 3 toxicity. Only 13 patients (9%) had late toxicities. At 24 months, the cumulative incidence of local failure was 7.4%. Median bPFS for the entire cohort was 12.9 months and 52% at 1 year. On multivariable analysis, factors associated with prolonged bPFS were peri-RT androgen deprivation therapy (ADT), lower gross tumor volume, and hormone-sensitive (HS) OPCa. Median time to next intervention, including repeat RT, was 21.6 months. Median bPFS for men with HS prostate cancer was 17.2 months compared with 7.2 months in men with castrate-resistant OPCa (P < .0001), and cumulative incidence of local failure at 24 months was lower with HS OPCa (4.8% vs 12.1%; P = .034). We analyzed 28 men with HS OPCa treated with a course of peri-RT ADT (median, 4.3 months) with recovery of testosterone. At a median follow-up of 33.5 months, 20 patients had not developed bPFS, median bPFS had not been reached, and 24-month bPFS was 77%. CONCLUSIONS: Metastasis-directed therapy can be effective across a wide range of OPCa subtypes, but with differential efficacy. Further study is warranted to investigate the use of RT across the wide range of patients with OPCa.

Bone mineral density loss in thoracic and lumbar vertebrae following radiation for abdominal cancers.

PURPOSE: To investigate the relationship between abdominal chemoradiation (CRT) for locally advanced cancers and bone mineral density (BMD) reduction in the vertebral spine. MATERIALS AND METHODS: Data from 272 patients who underwent abdominal radiation therapy from January 1997 to May 2015 were retrospectively reviewed. Forty-two patients received computed tomography (CT) scans of the abdomen prior to initiation and at least twice after radiation therapy. Bone attenuation (in Hounsfield unit) (HU) measurements were collected for each vertebral level from T7 to L5 using sagittal CT images. Radiation point dose was obtained at each mid-vertebral body from the radiation treatment plan. Percent change in bone attenuation (Δ%HU) between baseline and post-radiation therapy were computed for each vertebral body. The Δ%HU was compared against radiation dose using Pearson's linear correlation. RESULTS: Abdominal radiotherapy caused significant reduction in vertebral BMD as measured by HU. Patients who received only chemotherapy did not show changes in their BMD in this study. The Δ%HU was significantly correlated with the radiation point dose to the vertebral body (R=-0.472, P<0.001) within 4-8 months following RT. The same relationship persisted in subsequent follow up scans 9 months following RT (R=-0.578, P<0.001). Based on the result of linear regression, 5 Gy, 15 Gy, 25 Gy, 35 Gy, and 45 Gy caused 21.7%, 31.1%, 40.5%, 49.9%, and 59.3% decrease in HU following RT, respectively. Our generalized linear model showed that pre-RT HU had a positive effect (ß=0.830) on determining post-RT HU, while number of months post RT (ß=-0.213) and radiation point dose (ß=-1.475) had a negative effect. A comparison of the predicted versus actual HU showed significant correlation (R=0.883, P<0.001) with the slope of the best linear fit=0.81. Our model's predicted HU were within ±20 HU of the actual value in 53% of cases, 70% of the predictions were within ±30 HU, 81% were within ±40 HU, and 90% were within ±50 HU of the actual post-RT HU. Four of 42 patients were found to have vertebral body compression fractures in the field of radiation. CONCLUSIONS: Patients who receive abdominal chemoradiation develop significant BMD loss in the thoracic and lumbar vertebrae. Treatment-related BMD loss may contribute to the development of vertebral compression fractures. A predictive model for post-CRT BMD changes may inform bone protective strategies in patients planned for abdominal CRT.

Application and Dosimetric Requirements for Gallium-68-labeled Somatostatin Analogues in Targeted Radionuclide Therapy for Gastroenteropancreatic Neuroendocrine Tumors.

Neuroendocrine tumors (NETs) are associated with variable prognosis, with grade 1 and 2 NETs having more favorable outcomes than grade 3. Patients with gastroenteropancreatic (GEP)-NET need individualized interdisciplinary evaluations and treatment. New treatment options have become available with significant improvements in progression-free survival. Peptide receptor radionuclide therapy (PRRT) using (90)Y or (177)Lu-labeled somatostatin analogues (SSTa) has also shown promise in the treatment of advanced progressive NETs. (68)Ga-1,4,7,10-tetraazacyclodecane-1,4,7,10-tetraacetic acid (DOTA)-SSTa can be used as companion imaging agents to assist in radionuclide therapy selection. (68)Ga-DOTA-SSTa PET/computed tomography might also provide information for prognosis, tumor response assessment to PRRT, and internal dosimetry.

[Current situation and perspectives of proton therapy]. / État des lieux et perspectives de la protonthérapie.

Proton beam therapy is indicated as a treatment for some rare tumours and paediatric tumours because the technique allows a good local control with minimal toxicity; the growing number of centres that use proton beam therapy is associated with an increase of dosimetric and clinical data for other malignant tumours as well. This paper reviews potential indications of proton beam therapy. A systematic review on Medline was performed with the following keywords proton beam therapy, cancer, heavy particle, charged particle. No phase III trial has been published using proton beam therapy in comparison with the best photon therapy, but numerous retrospective and dosimetric studies have revealed an advantage of proton beam therapy compared to photons, above all in tumours next to parallel organs at risk (thoracic and abdominal tumours). This could be accompanied with a better safety profile and/or a better tumoural control; numerous phase 0, I, II, III and IV studies are ongoing to examine these hypotheses in more common cancers. Use of proton beam therapy is growing for common cancers within clinical trials but some indications could be applied sooner since in silico analysis showed major advantages with this technique.

Quantitative SPECT/CT Imaging of (177)Lu with In Vivo Validation in Patients Undergoing Peptide Receptor Radionuclide Therapy.

PURPOSE: The purpose of this study is to extend an established SPECT/CT quantitation protocol to (177)Lu and validate it in vivo using urine samples, thus providing a basis for 3D dosimetry of (177)Lu radiotherapy and improvement over current planar methods which improperly account for anatomical variations, attenuation, and overlapping organs. PROCEDURES: In our quantitation protocol, counts in images reconstructed using an ordered subset-expectation maximization algorithm are converted to kilobecquerels per milliliter using a calibration factor derived from a phantom experiment. While varying reconstruction parameters, we tracked the ratio of image to true activity concentration (recovery coefficient, RC) in hot spheres and a noise measure in a homogeneous region. The optimal parameter set was selected as the point where recovery in the largest three spheres (16, 8, and 4 ml) stagnated, while the noise continued to increase. Urine samples were collected following 12 SPECT/CT acquisitions of patients undergoing [(177)Lu]DOTATATE therapy, and activity concentrations were measured in a well counter. Data was reconstructed using parameters chosen in the phantom experiment, and estimated activity concentration from the images was compared to the urine values to derive RCs. RESULTS: In phantom data, our chosen parameter set yielded RCs in 16, 8, and 4 ml spheres of 80.0, 74.1, and 64.5 %, respectively. For patients, the mean bladder RC was 96.1 ± 13.2% (range, 80.6-122.4 %), with a 95 % confidence interval between 88.6 and 103.6 %. The mean error of SPECT/CT concentrations was 10.1 ± 8.3% (range, -19.4-22.4 %). CONCLUSIONS: Our results show that quantitative (177)Lu SPECT/CT in vivo is feasible but could benefit from improved reconstruction methods. Quantifying bladder activity is analogous to determining the amount of activity in the kidneys, an important task in dosimetry, and our results provide a useful benchmark for future efforts.

Peptide receptor radionuclide therapy with 177Lu-DOTATATE for patients with somatostatin receptor-expressing neuroendocrine tumors: the first US phase 2 experience.

OBJECTIVE: Peptide receptor radionuclide therapy with radiolabeled somatostatin analogs is a novel method of treatment in patients with metastatic neuroendocrine tumors (NETs). For the first time in the United States, we present preliminary results of the treatment with Lutetium (177)(Lu) DOTATATE in patients with progressive NETs. METHODS: Thirty-seven patients with grade 1 and grade 2 disseminated and progressive gastroenteropancreatic NET were enrolled in a nonrandomized, phase 2 clinical trial. Repeated cycles of 200 mCi (7.4 GBq; ±10%) were administered up to the cumulative dose of 800 mCi (29.6 GBq; ±10%). RESULTS: Among 32 evaluable patients, partial response and minimal response to treatment were seen in 28% and 3%, respectively, and stable disease was seen in 41% of patients. A total of 28% had progressive disease. A response to treatment was significantly associated with lower burden of disease in the liver. No significant acute or delayed hematologic or kidney toxicity was observed. An impressive improvement of performance status and quality of life were seen after Lu-DOTATATE therapy. CONCLUSIONS: Treatment with multiple cycles of (177)Lu-DOTATATE peptide receptor radionuclide therapy is well tolerated. This treatment results in control of the disease in most patients, whereas systemic toxicities are limited and reversible. Quality of life is also improved.

Individualized dosimetry-based activity reduction of 9°Y-DOTATOC prevents severe and rapid kidney function deterioration from peptide receptor radionuclide therapy.

PURPOSE: Assessment of kidney function evolution after (90)Y-DOTATOC peptide receptor radionuclide therapy (PRRT) with capped activity administration based on a 37-Gy threshold of biological effective dose (BED) to the kidney. METHODS: In a prospective phase II study, patients with metastasized neuroendocrine tumours were evaluated for therapy using 185 MBq (111)In-pentetreotide with amino acid coinfusion. Planar whole-body images were acquired at four time-points after injection and kidney volumes were measured using CT/MRI. BED to the kidneys was estimated using an extended BED formula and biexponential renal clearance. Based on published BED dose-toxicity relationships, we allowed a maximal kidney BED of 37 Gy; if the calculated BED exceeded 37 Gy, treatment activity was reduced accordingly. Kidney function was assessed at baseline and at 18 months, predominantly using (51)Cr-EDTA. The rate of renal function decline was expressed as annual glomerular filtration rate loss (aGFRL). RESULTS: Only 22 of 50 patients reached the 18-months time-point, with most missing patients having died due to disease progression. In the 22 patients who reached 18 months, no rapid kidney function deterioration was observed over the 18 months, aGFRL >33% was not seen, and only three patients showed an increase of one toxicity grade and one patient an increase of two grades. No significant correlations between kidney volume (p = 0.35), baseline GFR (p = 0.18), risk factors for renal function loss (p = 0.74) and aGFRL were observed. Among the 28 patients who did not reach 18 months, one developed grade 4 kidney toxicity at 15 months after PRRT. CONCLUSION: Prospective dosimetry using a 37 Gy BED as the threshold for kidney toxicity is a good guide for (90)Y-DOTATOC PRRT and is associated with a low risk of rapid renal function deterioration and evolution to severe nephrotoxicity.

Outcome and toxicity of salvage therapy with 177Lu-octreotate in patients with metastatic gastroenteropancreatic neuroendocrine tumours.

PURPOSE: We assessed the outcome and toxicity of salvage therapy (repeat treatment) with (177)Lu-octreotate and high cumulative activities in patients with metastatic gastroenteropancreatic neuroendocrine tumours (GEP-NET). METHODS: We retrospectively analysed a consecutive cohort of 33 patients with metastatic GEP-NET who underwent salvage peptide receptor radionuclide therapy (PRRT) in our institution. All patients had progressive NET prior to salvage treatment and had shown an initial response to PRRT. The mean cumulative activity was 44.3 GBq (30.0-83.7 GBq). Radiographic response was assessed using CT and/or MRI according to modified SWOG criteria. Toxicity was evaluated using laboratory data, including complete blood counts and renal function tests using CTCAE 3.0. Survival analysis was performed with the Kaplan-Meier curve method and a significance level at p < 0.05. RESULTS: Radiographic responses consisted of complete response in 1 patient (3.0%), partial response in 6 patients (18.2%), minor response in 1 patient (3.0%), stable disease in 14 patients (42.4%), and progressive disease in 11 patients (33.3%). Median progression-free survival (PFS) from the start of salvage therapy was 13 months (95% CI 9-18) and patients with a history of a durable PFS after initial PRRT tended to have long-lasting PFS after salvage treatment (p = 0.04). None of the patients developed severe nephrotoxicity (grade 3/4) or a myelodysplastic syndrome during follow-up. Relevant albeit reversible haematotoxicity (grade 3/4) occurred in 7 patients (21.2%). The cumulative administered activity was not associated with an increased incidence of haematotoxicity. CONCLUSION: PRRT with (177)Lu-octreotate in the re-treatment setting is safe and effective in patients with metastatic GEP-NET.

Efficacy of argon plasma coagulation in the treatment of radiation-induced hemorrhagic gastroduodenal vascular ectasia.

OBJECTIVE: Radiation-induced hemorrhagic gastroduodenal vascular ectasia (GDVE) is rare but difficult to manage. Argon plasma coagulation (APC) has not yet been evaluated in the treatment of radiation-induced hemorrhagic GDVE. The efficacy of APC in patients with radiation-induced hemorrhagic GDVE has been investigated in this article. MATERIAL AND METHODS: Eighteen patients with upper gastrointestinal (GI) bleeding caused by radiation-induced GDVE, including 13 with hepatocellular carcinoma, 3 with pancreatic cancer, and 2 with cholangiocarcinoma, were treated with APC. The efficacy of APC was retrospectively evaluated, based on cessation of macroscopic GI bleeding, resolution or stabilization of anemia and transfusion dependence, endoscopic ablation of almost all vascular lesions, complications, and recurrence. RESULTS: Mean patient age was 59 years (range 42-80 years). The median time from radiation to GDVE diagnosis was 4.6 months (range 3.3-21.5 months). The median number of APC sessions per patient was 2.4 (range 1-4). All 18 patients showed an endoscopic response to APC treatment, with sustained increases in mean hemoglobin level, from 6.6 g/dL (range 2.9-9.5 g/dL) to 9.7 g/dL (range 7.1-12.7 g/dL) (p < 0.001), and decreased dependence on transfusion, from 9.1 (range 0-30) to 4.1 (range 0-15) units of packed red blood cells per patient (p = 0.038) after last endoscopic eradication by APC treatment. There were no major procedure-related adverse events or deaths. At a median follow up of 4.7 months (range 0.6-24.5 months), none of the patients experienced recurrence of GDVE. CONCLUSIONS: APC showed short-term effectiveness and safety in the treatment of radiation-induced hemorrhagic GDVE.

Early prediction of tumour response to PRRT. The sequential change of tumour-absorbed doses during treatment with 177Lu-octreotate.

UNLABELLED: [177Lu-DOTA0,Tyr3]-octreotate (177Lu-octreotate) in peptide receptor radionuclide therapy (PRRT) offers direct intra-therapeutic dosimetry. The aim of this study was to compare tumour and non-tumour parameters and assess intra-individual variations. PATIENTS, METHODS: Retrospective analysis of 53 consecutive PRRT treatment cycles (mean activity of 7.53 ± 0.46 GBq 177Lu-octreotate, intended four cycles at intervals of 10-14 weeks, standard nephroprotection) in 27 GEP NET patients. Extended planar dosimetry with serial whole-body imaging on selected, non-superimposed tumour and non-tumour regions; liver (LM), bone (BM), and other (OM) metastases. The per-cycle variation was compared with post-treatment response (CT/MRI three months post-treatment, modified SWOG criteria). RESULTS: Residence time in tumor lesions (133-147 h) exceeded that in kidneys (93 h). Tumour-to-kidney absorbed dose ratios ranged from 14 to 28 (LM, BM, OM). Intra-individual per-cycle dose variation was insignificant for kidneys, but significant for metastases (LM, BM, and OM; p < 0.05). The mean per-cycle decrease of tumour absorbed dose (ΔD/A0[%]) was linked to morphologic response after PRRT. A mean decrease of >20% was predictive of a partial or minor remission in all 11 evaluable patients, while absent significant dose reduction indicated stable or progressive disease in 4/5 patients. The dose decrease was unrelated to volume effects and also observed for BM. CONCLUSION: Besides confirmation of a favourable tumour-to-kidney parameter relation for 177Lu-octreotate, stepwise intra-lesional comparison seems to imply a prognostic impact of tumor dosimetry: The early per-cycle change ΔD/A0 between treatment cycles may predict the outcome after PRRT. Larger studies are needed to confirm this finding.

Once-weekly stereotactic radiotherapy for patients with oligometastases: compliance and preliminary efficacy.

AIMS AND BACKGROUND: This retrospective analysis reports the outcomes obtained with an original once-weekly stereotactic radiotherapy fractionation given to patients affected by evolving oligometastases from different solid malignancies. METHODS: From 2009 to 2011, patients with symptomatic and/or evolving oligometastases were submitted to a median 5-fraction cycle of stereotactic radiotherapy of one fraction per week in order to exploit a radiobiological rationale designed to increase the therapeutic index. Individual fractionation was mainly planned according to patient performance status, oligometastasis size and site, and record of previous irradiation in the same site. RESULTS: Thirty-six patients in stage IV UICC-TNM affected by oligometastases were treated with image-guided intensity-modulated stereotactic tomotherapy with a single weekly radiation. Median age was 70 years (range, 34-89). The median weekly single dose, number of fractions and overall total radiation dose were 7 Gy, 5 fractions and 35 Gy, respectively. Thirty-five (97%) patients completed the treatment schedule. No patient suffered mild or severe radiation-related side effects. Twenty-one (87%) of 24 patients with local pain had complete symptomatic response within 30 days following the end of radiotherapy. Local control assessed at imaging after stereotactic radiotherapy was evidenced in 30 (83%) patients. Median time to response after the end of radiotherapy was 40 days. CONCLUSIONS: The original radiotherapy regimen delivering only a single stereotactic dose per week seems to be highly feasible with an interesting high efficacy rate in patients with oligometastases from different solid tumors. Overall, the once-weekly treatment was very compliant in an advanced cancer stage especially for elderly and frail patients.