Radiation therapy for the management of painful bone metastases: Results from a randomized trial

AimThe aim of this study was to compare the effectiveness of two radiotherapy schedules in patients with bone metastases.BackgroundWe analyzed the need for re-irradiation, rates of pain control, pathological fractures, and functionality in patients randomized to single-fraction (8 Gy 1×) or multiple-fraction radiotherapy (3 Gy 10×) with at least 12 months follow-up, during five years. The hypothesis was that the two radiotherapy schedules are equally effective.Materials and methodsNinety patients with painful skeletal metastases were randomized to receive single fraction (8 Gy) or multiple fraction (3 Gy 10×) radiotherapy.ResultsIn the single-fraction group, seven pathological fractures occurred (15.5%) versus two (4.4%) in the multiple-fraction group. There was no statistically significant difference between the time it took to suffer a pathological fracture in both groups (p = 0.099). Patients in the single-fraction group received twelve re-irradiations (26.6%), four in the multiple-fraction group (8.8%), with no significant difference between time elapsed before the first re-irradiation (p = 0.438).ConclusionThis study shows no difference between the two groups for the majority of patients with painful bone metastases. Patients were followed up during five years, and the trial showed no disadvantage for 8 Gy 1× compared to 3 Gy 10×. Despite the fact that the pathological fracture rate is 3.75 times higher in the single-fraction group, this schedule is considered more convenient for patients and more cost-effective for radiotherapy departments.     

Post-chemotherapy target volumes are safe as boost volume for intact breast radiotherapy in locally advanced breast cancer

PurposeThe purpose of our study is to evaluate the challenges in identification of postoperative complexes (POC), the utility of clips in delineation of clinical target volume for boost in LABC downstaged with neoadjuvant chemotherapy (NACT) and to correlate this with patterns of recurrence.Methods and materialsLABC patients who underwent NACT followed by BCS and radiotherapy (2007–2014) were the subject of our analysis. The data on visibility and characteristics of postoperative cavity (POC), concordance of its volume with clip volume on radiation planning scan were retrieved. A 1 cm margin beyond POC was delineated as a clinical target volume (CTV). Postoperative whole breast and supraclavicular radiotherapy (50 Gy/25fractions/5wk or 42.4 Gy/16#/3 wk) followed by boost (10−16 Gy/5-8#/1–1.5wk) were delivered. Patterns of recurrence were evaluated.ResultsOut of 60 patients, 28.3% patients had stage II disease and 71.7% had stage III disease. 25% patients achieved pathological CR (complete response). The median POC volume was 30 cc and the median clip volume was 40 cc. The concordance of POC volume with clip volume was seen in 80%. Clips served as a good surrogate for POC in 80% of patients. At a median follow-up of 65 months (IQ range 32–84 months), and a lost to follow-up rate of 11.6 %, 3.3% (n = 2) patients had local recurrence (LR) and 8.3% (n = 5) had regional recurrence (LRR) in the supraclavicular region.ConclusionsDelineation of post NACT excision cavity as POC for boost radiotherapy is safe. Clips serve as a good surrogate for CTV delineation in 75% patients.     

Image-guided brachytherapy in cervical cancer: Experience in the Complejo Hospitalario de Navarra

PurposeTo evaluate dosimetric and clinical findings of MRI-guided HDR brachytherapy (HDR-B) for cervical carcinoma.Material and methodsAll patients had a CT, MRI and pelvic-paraaortic lymphadenectomy. Treatment: pelvic (+/−)para-aortic3D/IMRT radiotherapy (45 Gy), weekly cisplatin and HDR-B and pelvic node/parametrial boost 60 Gy until interstitial brachytherapy was done. Two implants: 2008–2011: 5 fractions of 6 Gy, 2011: 2016, 4 fractions of 7 Gy. MRI/TAC were done in each implant. The following were defined: GTV, CTH-HR, CTV-IR; OAR: rectum, bladder and sigmoid.ResultsFrom 2007 to 2016: 57 patients. Patients: T1b2-T2a: 4p, T2b 41p, T3a: 2p; T3B 8p T4a: 2p; N0: 32p, N1 21p, no lymphadenectomy: 4p. Median follow up: 74.6 m (16–122 m), recurrence: 5p local, 6p node, 9p metastasis and 37p without recurrence.Local control 5 years: 90.1%; Ib2-IIB: 94.8%, III-IVa: 72.2%. (p:0.01). RDFS 5y was 92.5%; IB2-IIB: 93%, III: 85% (p:0.024); for pN0: 100%; pN+ iliac-paraaortic: 71.4% (p: 0.007). MFS 5y was 84.1%. Overall survival (OS) at 5y: 66.6% and the cancer specific survival (CEOS) was 74%. Univariate analysis survival: stage Ib2-II 83% vs. III-IVa 41% (p = 0.001); histology: squamous 78%, adenocarcinoma 59.7% (p: ns); lymph node: N0 85% vs. PA+P− 72%, and PA+P+ 35% (p = 0.010). In relation with: HR-CTV dose > 85 Gy, CEOS: 82.5% vs. 77%, and volume CTV-HR < 30 cc: 81.8% and >30 cc: 67%; p: ns. Acute grade 2–3 toxicity: rectal 15.7%, intestinal 15.7% and vesical 15.5%.ConclusionUse of interstitial HDR-BQ guided by RM increased CTV-HR dose and local control, like EMBRACE results. Nodal boost improves RDFS and perhaps OS.     

A dosimetric analysis comparing electron beam with the MammoSite brachytherapy applicator for intact breast boost

IntroductionElectron beam radiation is the modality most often used to deliver an operative bed boost to breast cancer patients after completing whole breast radiation. However, electrons can potentially provide inadequate coverage. The MammoSite breast brachytherapy applicator may provide dosimetric advantages in the delivery of an operative bed boost and its role in this setting is not yet defined.Materials and methodsThe study population consisted of 15 patients with early stage breast cancer treated with partial breast irradiation (PBI) using the MammoSite device. For each patient, a theoretical boost plan using electrons and a second theoretical boost plan using the MammoSite applicator were created. To assess the adequacy of each boost plan, the PTV V90, PTV V95, and PTV V100 were calculated. To assess dose to normal tissues, the ipsilateral breast V50, ipsilateral lung V30, and heart V20 were calculated.ResultsThe mean PTV V100 for the MammoSite boost was 95.5%, compared to 77.4% for the electron boost (p < 0.001). The mean PTV V95 was 97.8%, compared to 93.3% for the electron boost (p = 0.02). The mean PTV V90, mean breast V50, mean lung V30, and mean heart V20 were not statistically different for MammoSite compared to electrons.ConclusionsA tumor bed boost using the MammoSite breast brachytherapy applicator provides superior target coverage and delivers similar doses to the ipsilateral breast and lung compared to a boost delivered with electrons. More investigation into the role of balloon brachytherapy in the delivery of a breast boost is warranted.     

Luminal (Her2 negative) prognostic index and survival of breast cancer patients

PurposeThe group of luminal (Her2 negative) is distinguished from other subtypes of breast cancer. We aimed to produce a prognostic index specific for luminal (Her2 negative) subtype breast cancer that could assist clinical treatment.MethodsThe test set comprised 406 consecutive luminal (Her2 negative) breast cancer patients. The relationship of 11 clinicopathologic factors including survivin with the 5-year disease-free survival was analyzed.ResultsIn univariate analysis, TNM stage, surgery, tumor size, lymph node involvement, and survivin expression were prognostic factors. In multivariate analysis, tumor size [HR (95% CI): 1.98 (1.12–3.49), p = 0.019], the number of lymph node metastasis [HR (95% CI): 1.75 (1.33–2.29), p < 0.0001] and the expression of progesterone receptor [HR (95% CI): 0.58 (0.36–0.95), p = 0.029] can independently predict prognosis. Prognostic index (PI) was calculated as 0.68 × tumor size + 0.56 × the number of lymph node metastasis − 0.54 × PR. According to the PI, patients were categorized into three groups: low, middle, and high risk group with the 5-year disease-free survival rates of 91.91%, 84.97% and 70.47%, respectively (P < 0.001). In the validation set, the luminal prognostic index (LPI) remained significant.ConclusionThe LPI may be a useful tool for evaluating the outcome of patients with luminal (Her-2 negative) breast cancer.     

Is the lack of respiratory gating prejudicial for left breast TomoDirect treatments?

Background and purposeTomoDirect (TD) can only operate in free-breathing. The purpose of this study is to compare TD with breath-hold 3D conformal radiotherapy (3DCRT) and intensity modulated radiotherapy (IMRT) techniques for left breast treatments, and to determine if the lack of respiratory gating is a handicap for cardiac sparing.Materials and methods15 patients treated for left breast had two computed tomography simulation, in free breathing (FB) and in deep-inspiration breath-hold (DIBH). Four treatments were planned: TD-FB, 3DCRT-FB, 3DCRT-DIBH and IMRT-DIBH. Dose to PTV, heart, lungs, right breast and patient were compared.ResultsA slightly lower cardiac mean dose is found for 3DCRT-DIBH than for TD-FB group (1.99 Gy Vs 2.89 Gy, p = 0.0462), while no statistical difference is found for heart V₂₀. TD-FB plans show the best PTV dose homogeneity (0.053, p < 0.001) and the lowest left lung mean dose (5.16 Gy, p < 0.001). No major differences are found for the other organs.ConclusionsTomoDirect and breath-hold 3DCRT are complementary techniques for left breast treatments: for a minority of patients, respiratory gating is mandatory to lower cardiac dose; for the remaining majority of patients, TomoDirect achieves better PTV homogeneity and reduced left lung dose, with cardiac dose equivalent to 3DCRT-DIBH.     

Stereotactic body radiation therapy in hepatocellular carcinoma: Optimal treatment strategies based on liver segmentation and functional hepatic reserve

AimTo discuss current dosage for stereotactic body radiation therapy (SBRT) in hepatocellular carcinoma (HCC) patients and suggest alternative treatment strategies according to liver segmentation as defined by the Couinaud classification.BackgroundSBRT is a safe and effective alternative treatment for HCC patients who are unable to undergo liver ablation/resection. However, the SBRT fractionation schemes and treatment planning strategies are not well established.Materials and methodsIn this article, the latest developments and key findings from research studies exploring the efficacy of SBRT fractionation schemes for treatment of HCC are reviewed. Patients’ characteristics, fractionation schemes, treatment outcomes and toxicities were compiled. Special attention was focused on SBRT fractionation approaches that take into consideration liver segmentation according to the Couinaud classification and functional hepatic reserve based on Child–Pugh (CP) liver cirrhosis classification.ResultsThe most common SBRT fractionation schemes for HCC were 3 × 10–20 Gy, 4–6 × 8–10 Gy, and 10 × 5–5.5 Gy. Based on previous SBRT studies, and in consideration of tumor size and CP classification, we proposed 3 × 15–25 Gy for patients with tumor size <3 cm and adequate liver reserve (CP-A score 5), 5 × 10–12 Gy for patients with tumor sizes between 3 and 5 cm or inadequate liver reserve (CP-A score 6), and 10 × 5–5.5 Gy for patients with tumor size >5 cm or CP-B score.ConclusionsTreatment schemes in SBRT for HCC vary according to liver segmentation and functional hepatic reserve. Further prospective studies may be necessary to identify the optimal dose of SBRT for HCC.     

A new split arc VMAT technique for lymph node positive breast cancer

PurposeTo investigate different volumetric modulated arc therapy (VMAT) field designs for lymph node positive breast cancer patients when compared to conventional static fields and standard VMAT designs.MethodsNineteen breast cancer patients with lymph node involvement (eleven left and eight right sided) were retrospectively analyzed with different arc designs. Proposed split arc designs with total rotations of 2 × 190° and 2 × 240° were compared to conventional field in field (FinF) and previously published non-split arc techniques with the same amount of total rotations.ResultsAll VMAT plans were superior in dose conformity, when compared to the FinF plans. Split arc design decreased significantly ipsilateral lung dose and heart V5Gy for both left and right sided cases, when compared to non-split VMAT designs. For left sided cases no significant differences were seen in contralateral lung mean dose or V5Gy between different VMAT designs. For right sided cases the contralateral lung dose V5Gy was significantly higher in split VMAT group, when compared to non-split VMAT designs. The contralateral breast dose V5Gy increased significantly for split VMAT plans for both sides, when compared to non-split VMAT designs or FinF plans.ConclusionsThe proposed split VMAT technique was shown to be superior to previously published non-split VMAT and conventional FinF techniques significantly reducing dose to the ipsilateral lung and heart. However, this came with the expense of an increase in the dose to the contralateral breast and for right-sided cases to the contralateral lung.     

Copper,selenium and zinc levels after bariatric surgery in patients recommended to take multivitamin-mineral supplementation

BackgroundBariatric surgery is widely performed to improve obesity-related disorders, but can lead to nutrient deficiencies. In this study we examined serum trace element concentrations before and after bariatric surgery.MethodsWe obtained serum trace element concentrations by inductively coupled plasma-mass spectrometry (ICP-MS) method in 437 patients (82% women, median preoperative body-mass index 46.7 kg/m² [interquartile range 42–51]) undergoing either gastric banding (22.7%), sleeve gastrectomy (20.1%), or gastric bypass (57.3%) procedures. Trace element data were available for patients preoperatively (n = 44); and 3 (n = 208), 6 (n = 174), 12 (n = 122), 18 (n = 39), 24 (n = 44) and 36 months (n = 14) post-operatively. All patients were recommended to take a multivitamin-mineral supplement after surgery.ResultsCopper deficiency was found in 2% of patients before surgery; and after surgery deficiency rates ranged from 0 to 5% with no significant change in median concentrations during follow-up (p = 0.68). Selenium deficiency was reported in 2% of patients before surgery; and after surgery deficiency rates ranged from 11 to 15% with a near-significant change in median concentrations (p = 0.056). Zinc deficiency was reported in 7% before surgery; and after surgery deficiency rates ranged from 7 to 15% with no significant change in median concentrations (p = 0.39).ConclusionsIn bariatric surgery patients recommended to take multivitamin-mineral supplements, serum copper, zinc and selenium concentrations were mostly stable during the first years after bariatric surgery. There was a possible tendency for selenium concentrations to decline during the early postoperative period.     

Évaluation par la TEMP–TDM des lésions classées indéterminées en scintigraphie osseuse chez les patients de cancérologie

The aim of the present study was to investigate the contribution of the single photon emission computed tomography/computed tomography (SPECT/CT) in cancer patients and to evaluate its ability to correctly classify indeterminate lesions on planar bone scintigraphy (PBS).MethodsFrom November 2006 to August 2007, all patients with confirmed malignancy, whose PBS showed indeterminate lesions, underwent without delay a SPECT/CT. The study included 120 patients (67 men, 53 women), with a mean age of 69 ± 12 years (range 42–96 years). The patients with obvious metastases, important pains or who did not accept the examination were excluded from the study. The location of the lesions was described either as precise, probable or indeterminate. The lesions were classified either as definitely malignant, definitely benign or indeterminate.ResultsBreast, prostate, lung and kidney neoplasms represented approximately 80% of all cancers. The PBS highlighted 267 lesions of location either as precise (n = 29), probable (n = 129) or indeterminate (n = 109), classified either as definitely malignant (n = 28), definitely benign (n = 27) or indeterminate (n = 212). The SPECT/CT revealed 440 lesions, of location either as precise (n = 353), likely (n = 39) or indeterminate (n = 48), classified either as definitely malignant (n = 84), definitely benign (n = 305) or indeterminate (n = 51). Thoracic and lumbar spine and pelvis were the locations of 79% of the scintigraphic lesions and of 88% of the osseous metastases. SPECT/CT modified the final report of 80 patients, by excluding from metastases (n = 2), by showing metastases (n = 23) and by showing the benign character of indeterminate lesions (n = 55). Moreover, 69 patients out of 120 (> 57%) had an evolution confirmed with 35 true positives, 31 true negatives, one false negative and two patients with indeterminate lesions on SPECT/CT, without osseous metastasis.ConclusionThe assessment of the indeterminate scintigraphic lesions of oncologic patients benefits from the SPECT/CT. The lesion-based analysis showed that the SPECT/CT detected more lesions (+64%) and correctly classified 88% of the detected lesions. The patient-based analysis highlighted that SPECT/CT modified the final report for more than 66% of the patients. The follow-up showed that SPECT/CT correctly classified for more than 95% of the patients.     

Liquid chromatography–tandem mass spectrometry assay for the quantification of free and total sialic acid in human cerebrospinal fluid

BackgroundAnalysis of sialic acid (SA) metabolites in cerebrospinal fluid (CSF) is important for clinical diagnosis. In the present study, a high-performance liquid chromatography–tandem mass spectrometry (HPLC/MS/MS) method for free sialic acid (FSA) and total sialic acid (TSA) in human CSF was validated.MethodsThe method utilized a simple sample-preparation procedure of protein precipitation for FSA and acid hydrolysis for TSA. Negative electrospray ionisation was used to monitor the transitions m/z 308.2 → 87.0 (SA) and m/z 311.2 → 90.0 (¹³C₃-SA). Conjugated sialic acid (CSA) was calculated by subtracting FSA from TSA. We established reference intervals for FSA, TSA and CSA in CSF in 217 control subjects. The method has been applied to patients’ samples with known differences in SA metabolites like meningitis (n = 6), brain tumour (n = 2), leukaemia (n = 5), and Salla disease (n = 1).ResultsLimit of detection (LOD) was 0.54 μM for FSA and 0.45 μM for TSA. Intra- and inter-assay variation for FSA (21.8 μM) were 4.8% (n = 10) and 10.4% (n = 40) respectively. Intra- and inter-assay variation for TSA (35.6 μM) were 9.7% (n = 10) and 12.8% (n = 40) respectively. Tested patients showed values of TSA above established reference value.ConclusionThe validated method allows sensitive and specific measurement of SA metabolites in CSF and can be applied for clinical diagnoses.     

Possibility of limiting the un-justified irradiation in 131I therapy of Graves' disease: A thyroid mass-reduction based method for the optimum activity calculation

ObjectiveIn Graves' disease therapy, the amount of ¹³¹I is usually decided following two different modalities: the administration of a fixed activity or of an activity individually calculated based on a fixed value of target absorbed dose. Although the effectiveness of each of these approaches is good (about 80% of patients cured), the ALARA principle must be applied avoiding the un-justified radioactivity to the patient himself, the people living/working near him and the environment. In this paper a new approach to the ¹³¹I therapy in Graves' disease, based on the optimum value of the final thyroid mass, is presented.Design97 Graves' disease patients (29 males) were randomly assigned into three groups (GR1, GR2, GR3). In two of them (GR1, GR3) the radioiodine administering activity was calculated based on two fixed thyroid absorbed dose values (100 Gy for GR1; 400 Gy for GR3), in GR2 it was calculated based on the desired final optimum thyroid mass value m_f = 0.24 m₀/U₀ResultsThe rate of cured patients are 48% (GR1), 97% (GR2) (z-test, p < 0.001) and 97% (GR3). The average activity administered to GR2 (393 ± 157 MBq) is lower than that administrered to GR3 patients (524 ± 201 MBq) (p = 0.007, two-tails unpaired t-test); the thyroid absorbed dose in GR2 (262 ± 78 Gy) is lower than in GR3 patients (407 ± 23 Gy) (p < 0.001, two-tails unpaired t-test).ConclusionOur results demonstrate that the thyroid-mass based approach optimizes the treatment avoiding an un-justified excess or a not-effective too low activity without time and resources consuming.     

Immune mobilization of autologous blood progenitor cells: direct influence on the cellular subsets collected

Background aimsA phase I trial examined the ability of immunotherapy to mobilize progenitor and activated T cells.MethodsInterleukin (IL)-2 was administered subcutaneously for 11 days, with granulocyte (G)-colony-stimulating factor (CSF) (5 mcg/kg/day) and granulocyte–macrophage (GM)-CSF (7.5 mcg/kg/day) added for the last 5 days. Leukapheresis was initiated on day 11. Thirteen patients were treated (myeloma n = 11, non-Hodgkin's lymphoma n = 2).ResultsToxicities were minimal. IL-2 was stopped in two patients because of capillary leak (n = 1) and diarrhea (n = 1). Each patient required 2.5 leukaphereses (median; range 1–3) to collect 3.2 × 10⁶ CD34⁺ cells/kg (median; range 1.9–6.6 × 10⁶/kg). Immune mobilization increased the number of CD3⁺ CD8⁺ T cells (P = 0.002), CD56⁺ natural killer (NK) cells (P = 0.0001), CD8⁺ CD56⁺ T cells (P = 0.002) and CD4⁺ CD25⁺ cells (P = 0.0001) compared with cancer patients mobilized with G-CSF alone. There was increased lysis of myeloma cells after 7 days (P = 0.03) or 11 days (P = 0.02). The maximum tolerated dose of IL-2 was 1 × 10⁶ IU/m²/day.ConclusionsImmune mobilization is well tolerated with normal subsequent marrow engraftment. As cells within the graft influence lymphocyte recovery, an increased number of functional lymphocytes may result in more rapid immune reconstitution.     

A study on conventional IMRT and RapidArc treatment planning techniques for head and neck cancers

AimTo evaluate the performance of volumetric arc modulation with RapidArc against conventional IMRT for head and neck cancers.BackgroundRapidArc is a novel technique that has recently been made available for clinical use. Planning study was done for volumetric arc modulation with RapidArc against conventional IMRT for head and neck cancers.Materials and methodsTen patients with advanced tumors of the nasopharynx, oropharynx, and hypopharynx were selected for the planning comparison study. PTV was delineated for two different dose levels and planning was done by means of simultaneously integrated boost technique. A total dose of 70 Gy was delivered to the boost volume (PTV boost) and 57.7 Gy to the elective PTV (PTV elective) in 35 equal treatment fractions. PTV boost consisted of the gross tumor volume and lymph nodes containing visible macroscopic tumor or biopsy-proven positive lymph nodes, whereas the PTV elective consisted of elective nodal regions. Planning was done for IMRT using 9 fields and RapidArc with single arc, double arc. Beam was equally placed for IMRT plans. Single arc RapidArc plan utilizes full 360° gantry rotation and double arc consists of 2 co-planar arcs of 360° in clockwise and counter clockwise direction. Collimator was rotated from 35 to 45° to cover the entire tumor, which reduced the tongue and groove effect during gantry rotation. All plans were generated with 6 MV X-rays for CLINAC 2100 Linear Accelerator. Calculations were done in the Eclipse treatment planning system (version 8.6) using the AAA algorithm.ResultsDouble arc plans show superior dose homogeneity in PTV compared to a single arc and IMRT 9 field technique. Target coverage was almost similar in all the techniques. The sparing of spinal cord in terms of the maximum dose was better in the double arc technique by 4.5% when compared to the IMRT 9 field and single arc techniques. For healthy tissue, no significant changes were observed between the plans in terms of the mean dose and integral dose. But RapidArc plans showed a reduction in the volume of the healthy tissue irradiated at V_15 Gy (5.81% for single arc and 4.69% for double arc) and V_20 Gy (7.55% for single arc and 5.89% for double arc) dose levels when compared to the 9-Field IMRT technique. For brain stem, maximum dose was similar in all the techniques. The average MU (±SD) needed to deliver the dose of 200 cGy per fraction was 474 ± 80 MU and 447 ± 45 MU for double arc and single arc as against 948 ± 162 MU for the 9-Field IMRT plan. A considerable reduction in maximum dose to the mandible by 6.05% was observed with double arc plan. Double arc shows a reduction in the parotid mean dose when compared with single arc and IMRT plans.ConclusionRapidArc using double arc provided a significant sparing of OARs and healthy tissue without compromising target coverage compared to IMRT. The main disadvantage with IMRT observed was higher monitor units and longer treatment time.     

Evaluación de la utilidad diagnóstica de la biopsia ungueal en las onicomicosis

BackgroundOnychomycosis affects between 2% to 30% of the world population. Nail biopsy may help in making a diagnosis and can distinguish between invasion and colonisation.AimsTo evaluate the diagnostic usefulness of nail biopsy with Periodic acid–Schiff (PAS) staining for onychomycosis, compared to direct KOH examination, culture and its combination in a reference laboratory in Colombia.MethodsThe study included 66 patients in whom a blind and independent reading of the three tests was performed. The usefulness was defined based on the validity (sensitivity, specificity, Youden's index, likelihood ratios), performance (predictive values) efficiency (proportion of correctly diagnosed patients), and reproducibility (kappa coefficient).ResultsThe mean age of the patients was 55 ± 16 years, and included 76% women. The direct tests with KOH were positive in 66.7% (n = 44), 62.1% (n = 41) were positive with culture, and 56.1% (n = 37) with the biopsy. The main causal agents were non-dermatophytes moulds in 36.4% (n = 24). The most frequent species were Neoscytalidium dimidiatum (n = 11), Trichophyton rubrum (n = 11), and Candida parapsilosis (n = 13). The sensitivity of nail biopsy, when compared to the standard (KOH and/or culture), was 71%, specificity 83%, Youden's index 0.54, positive likelihood ratio 4.25, negative likelihood ratio 0.35, positive predictive value 92%, negative predictive value 52%, efficiency 74% and kappa coefficient 0.45. When biopsy was evaluated only in patients with onycholysis of the nail plate greater than 50%, all the parameters of diagnostic usefulness increased.ConclusionsThe overall usefulness of the biopsy was moderate for patients with more severe symptomatology, which makes its use advisable in cases of extensive onycholysis, and when discriminating colonisation from invasion is required.     

A phase II study of allogeneic natural killer cell therapy to treat patients with recurrent ovarian and breast cancer

BackgroundNatural killer (NK) cells derived from patients with cancer exhibit diminished cytotoxicity compared with NK cells from healthy individuals. We evaluated the tumor response and in vivo expansion of allogeneic NK cells in recurrent ovarian and breast cancerMethodsPatients underwent a lymphodepleting preparative regimen: fludarabine 25 mg/m² × 5 doses, cyclophosphamide 60 mg/kg × 2 doses, and, in seven patients, 200 cGy total body irradiation (TBI) to increase host immune suppression. An NK cell product, from a haplo-identical related donor, was incubated overnight in 1000 U/mL interleukin (IL)-2 prior to infusion. Subcutaneous IL-2 (10 MU) was given three times/week × 6 doses after NK cell infusion to promote expansion, defined as detection of ≥100 donor-derived NK cells/μL blood 14 days after infusion, based on molecular chimerism and flow cytometryResultsTwenty (14 ovarian, 6 breast) patients were enrolled. The median age was 52 (range 30–65) years. Mean NK cell dose was 2.16 × 10⁷cells/kg. Donor DNA was detected 7 days after NK cell infusion in 9/13 (69%) patients without TBI and 6/7 (85%) with TBI. T-regulatory cells (Treg) were elevated at day +14 compared with pre-chemotherapy (P = 0.03). Serum IL-15 levels increased after the preparative regimen (P = < 0.001). Patients receiving TBI had delayed hematologic recovery (P = 0.014). One patient who was not evaluable had successful in vivo NK cell expansionConclusionsAdoptive transfer of haplo-identical NK cells after lymphodepleting chemotherapy is associated with transient donor chimerism and may be limited by reconstituting recipient Treg cells. Strategies to augment in vivo NK cell persistence and expansion are needed.     

Local control rates in stereotactic body radiotherapy (SBRT) of lung metastases associated with the biologically effective dose

AimTo evaluate dose differences in lung metastases treated with stereotactic body radiotherapy (SBRT), and the correlation with local control, regarding the dose algorithm, target volume and tissue density.BackgroundSeveral studies showed excellent local control rates in SBRT for lung metastases, with different fractionation schemes depending on the tumour location or size. These results depend on the dose distributions received by the lesions in terms of the tissue heterogeneity corrections performed by the dose algorithms.Materials and methodsForty-seven lung metastases treated with SBRT, using intrafraction control and respiratory gating with internal fiducial markers as surrogates (ExacTrac, BrainLAB AG), were calculated using Pencil Beam (PB) and Monte Carlo (MC) (iPlan, BrainLAB AG).Dose differences between both algorithms were obtained for the dose received by 99% (D_99%) and 50% (D_50%) of the planning treatment volume (PTV). The biologically effective dose delivered to 99% (BED_99%) and 50% (BED_50%) of the PTV were estimated from the MC results. Local control was evaluated after 24 months of median follow-up (range: 3–52 months).ResultsThe greatest variations (40.0% in ΔD_99% and 38.4% in ΔD_50%) were found for the lower volume and density cases. The BED_99% and BED_50% were strongly correlated with observed local control rates: 100% and 61.5% for BED_99% > 85 Gy and <85 Gy (p < 0.0001), respectively, and 100% and 58.3% for BED_50% > 100 Gy and <100 Gy (p < 0.0001), respectively.ConclusionsLung metastases treated with SBRT, with delivered BED_99% > 85 Gy and BED_50% > 100 Gy, present better local control rates than those treated with lower BED values (p = 0.001).     

Biochemical relapse free survival rate in patients with prostate cancer treated with external radiotherapy: outcomes obtained at the CMN Siglo XXI Hospital de Oncología,CMN 20 de Noviembre and Hospital General de México of the México City

AimBiochemical relapse-free survival (bRFS) rate is determined by a cohort of Mexican patients (n = 595) with prostate cancer who received treatment with external radiotherapy.BackgroundPatients with prostate cancer were collected from CMN Siglo XXI (IMSS), CMN 20 de Noviembre (ISSSTE), and Hospital General de México (HGM). For the IMSS, 173 patients that are treated with three-dimensional conformal radiation therapy (3D-CRT) and 250 with SBRT, for the ISSSTE 57 patients are treated with 3D-CRT and on the HGM 115 patients are managed with intensity modulated radiation therapy (IMRT). The percentage of patients by risk group is: low 11.1%, intermediate 35.1% and high 53.8%. The average follow-up is 39 months, and the Phoenix criterion was used to determine the bRFS.Materials and methodsThe Kaplan–Meier technique for the construction of the survival curves and, the Cox proportional hazards to model the cofactors.Results(a) The bRFS rates obtained are 95.9% for the SBRT (7 Gy fx, IMSS), 94.6% for the 3D-CRT (1.8 Gy fx, IMSS), 91.3% to the 3D-CRT (2.65 Gy fx, IMSS), 89.1% for the SBRT (7.25 Gy fx, IMSS), 88.7% for the IMRT (1.8 Gy fx, HGM) %, and 87.7% for the 3D-CRT (1.8 Gy fx, ISSSTE). (b) There is no statistically significant difference in the bRFS rates by fractionation scheme, c) Although the numerical difference in the bRFS rate per risk group is 95.5%, 93.8% and 89.1% for low, intermediate and high risk, respectively, these are not statistically significant.ConclusionsThe RT techniques for the treatment of PCa are statistically equivalent with respect to the bRFS rate. This paper confirms that the bRFS rates of Mexican PCa patients who were treated with conventional vs. hypofractionated schemes do not differ significantly.