A three-dimensional printed customized bolus: adapting to the shape of the outer ear.

BACKGROUND: The skin-sparing effect of megavoltage-photon beams in radiotherapy (RT) reduces the target coverage of superficial tumours. Consequently, a bolus is widely used to enhance the target coverage for superficial targets. This study evaluates a three-dimensional (3D)-printed customized bolus for a very irregular surface, the outer ear. MATERIALS AND METHODS: We fabricated a bolus using a computed tomography (CT) scanner and evaluated its efficacy. The head of an Alderson Rando phantom was scanned with a CT scanner. Two 3D boluses of 5- and 10-mm thickness were designed to fit on the surface of the ear. They were printed by the Stratasys Objet260 Connex3 using the malleable "rubber-like" photopolymer Agilus. CT simulations of the Rando phantom with and without the 3D and commercial high density boluses were performed to evaluate the dosimetric properties of the 3D bolus. The prescription dose to the outer ear was 50 Gy at 2 Gy/fraction. RESULTS: We observed that the target coverage was slightly better with the 3D bolus of 10mm compared with the commercial one (D98% 98.2% vs. 97.6%).The maximum dose was reduced by 6.6% with the 3D bolus and the minimum dose increased by 5.2% when comparing with the commercial bolus. In addition, the homogeneity index was better for the 3D bolus (0.041 vs. 0.073). CONCLUSION: We successfully fabricated a customized 3D bolus for a very irregular surface. The target coverage and dosimetric parameters were at least comparable with a commercial bolus. Thus, the use of malleable materials can be considered for the fabrication of customized boluses in cases with complex anatomy.

A data mining based clinical decision support system for survival in lung cancer.

BACKGROUND: A clinical decision support system (CDSS ) has been designed to predict the outcome (overall survival) by extracting and analyzing information from routine clinical activity as a complement to clinical guidelines in lung cancer patients. MATERIALS AND METHODS: Prospective multicenter data from 543 consecutive (2013-2017) lung cancer patients with 1167 variables were used for development of the CDSS. Data Mining analyses were based on the XGBoost and Generalized Linear Models algorithms. The predictions from guidelines and the CDSS proposed were compared. RESULTS: Overall, the highest (> 0.90) areas under the receiver-operating characteristics curve AUCs for predicting survival were obtained for small cell lung cancer patients. The AUCs for predicting survival using basic items included in the guidelines were mostly below 0.70 while those obtained using the CDSS were mostly above 0.70. The vast majority of comparisons between the guideline and CDSS AUCs were statistically significant (p < 0.05). For instance, using the guidelines, the AUC for predicting survival was 0.60 while the predictive power of the CDSS enhanced the AUC up to 0.84 (p = 0.0009). In terms of histology, there was only a statistically significant difference when comparing the AUCs of small cell lung cancer patients (0.96) and all lung cancer patients with longer (≥ 18 months) follow up (0.80; p < 0.001). CONCLUSIONS: The CDSS successfully showed potential for enhancing prediction of survival. The CDSS could assist physicians in formulating evidence-based management advice in patients with lung cancer, guiding an individualized discussion according to prognosis.

Sinonasal squamous cell carcinoma without clinical lymph node involvement : Which neck management is best?

OBJECTIVES: The purpose of this work was to report outcomes of patients with nonmetastatic sinonasal squamous cell carcinoma (SNSCC) and to discuss the impact of elective neck irradiation (ENI) and selective neck dissection (SND) in clinically negative lymph node (N0) patients. METHODS: Data from 104 nonmetastatic SNSCC patients treated with curative intent were retrospectively analysed. Uni- and multivariate analyses were used to assess prognostic factors of overall survival (OS) and locoregional control (LRC). RESULTS: Median follow-up was 4.5 years. Eighty-five percent of tumours were stage III-IV. Treatments included induction chemotherapy (52.9 %), surgery (72 %) and radiotherapy (RT; 87 %). The 5­year OS, progression-free survival, and LRC rates were 48, 44 and 57 %, respectively. Absence of surgery predicted a decrease of OS (hazard ratio [HR] 2.6; 95 % confidence interval [CI] 1.4-4.7), and LRC (HR 3.5; 95 % CI 1.8-6.8). Regional relapse was observed in 13/104 (13 %) patients and most common sites were level II (n = 12; 70.6 %), level III (n = 5; 29.4 %) and level Ib (n = 4; 23.5 %). Management of the neck in N0 patients (n = 87) included 11 % SND alone, 32 % ENI alone, 20 % SND + ENI and 37 % no neck treatment. In this population, a better LRC was found according to the management of the neck in favour of SND (94 % vs. 47 %; p = 0.002) but not ENI. CONCLUSION: SND may detect occult cervical positive nodes, allowing selective postoperative RT. ENI (ipsilateral level II, ±Ib and III or bilateral) needs to be proposed in selected patients, especially when SND has not been performed.

Clinical outcomes of definitive chemoradiation followed by intracavitary pulsed-dose rate image-guided adaptive brachytherapy in locally advanced cervical cancer.

OBJECTIVE: To report the outcomes and late toxicities of patients with locally advanced cervical cancer treated with concomitant chemoradiation (CRT) followed by intracavitary image-guided adaptive brachytherapy (IGABT). METHODS: Data from consecutive patients with histologically proven stage IB-IVA cervical cancer treated with curative intent in a single institution were analyzed. After pelvic +/- para-aortic external-beam radiation therapy, they received pulsed-dose rate IGABT following GEC-ESTRO recommendations. RESULTS: Two hundred and twenty-five patients were enrolled. Sixty-five percent were stage≥IIB according to FIGO classification. Ninety-five percent received CRT. Mean D90 to HR and IR-CTV were 80.4+/-10.3Gy and 67.7+/-6.1Gy. After a median follow-up of 38.8months, 3-year local control and overall survival rates were 86.4% and 76.1%, respectively. A trend for a detrimental effect of tumor stage on local control rates was observed with 3-year local control rates of 100% for stages IB1 and IIA, 90.5 for IB2, 85.8% for IIB, 50% for IIIA, 77.1 for IIIB, and 66.7% for IVA tumors (p=0.06). Local control rates at 3years were 95.6% in the group of patients with D90 of HR-CTV≥85Gy, 88.8% in those with D90 between 80 and 85Gy, and 80% when D90<80Gy (p=0.018). Eighteen severe late gastrointestinal and urinary effects affecting 14 patients were reported corresponding with a crude incidence of 6.6%. CONCLUSIONS: CRT followed by IGABT provides high local control rates with limited toxicity. Reaching high doses is mandatory to achieve local control and interstitial brachytherapy is necessary in advanced diseases.

Prognostic value of the TGFß1 rs4803455 single nucleotide polymorphism in small cell lung cancer.

BACKGROUND: Small cell lung cancer (SCLC) is one of the greatest therapeutic challenges of oncology. Potential associations between single nucleotide polymorphisms in heat shock protein ß1 (HSPB1) and transforming growth factor ß1 (TGFß1) and survival have been investigated. METHODS: A prospective multicenter study of 94 patients with SCLC treated between 2013 and 2016 was conducted. Clinical, tumour-related, therapeutic, and genetic (9 SNPs of TGFß1 gene and 5 of HSPB1 gene) variables were analyzed. RESULTS: The cohort included 77 men and 17 women with a median age of 61 years. Eighty percent presented with limited stage at diagnosis and received thoracic radiation with a median dose of 45 Gy (twice-daily radiation in 42%). Forty-seven percent received concurrent platinum-based chemotherapy and 57% received prophylactic cranial irradiation (PCI). Overall survival (OS) was 34% at 2 years and 16% at 3 years. In multivariate analysis, the rs4803455:CA genotype of the TGFß1 gene showed a statistically significant association with lower disease-free survival (DFS; hazard ratio [HR] 3.13; confidence interval [CI] 1.19-8.17; p = 0.020) and higher local recurrence (HR 3.80; CI 1.37-10.5; p = 0.048), and a marginal association with lower OS (HR 1.94; CI 0.98-3.83; p = 0.057). A combined analysis showed that patients receiving PCI and carrying the rs4803455:CA genotype had statistically significant lower OS (p < 0.001) and DFS (p < 0.001) than patients receiving PCI and carrying the rs4803455:AA genotype. CONCLUSIONS: Genetic analysis showed the CA genotype of TGFß1 SNP rs4803455 was associated with worse prognosis in patients with SCLC and could be considered as a potential biomarker.

High dose rate brachytherapy for prostate cancer: A prospective toxicity evaluation of a one day schedule including two 13.5 Gy fractions.

BACKGROUND AND PURPOSE: High dose-rate (HDR) brachytherapy (BT) provides a highly conformal method of dose delivery to the prostate. The purpose of this study is to prospectively determine the toxicity of the treatment protocol of 13.5 Gy × 2 fractions. MATERIALS AND METHODS: From 2010 through 2017, 119 patients with low (71%) or intermediate-risk prostate cancer were prospectively treated in a single institute with HDR-BT at 13.5 Gy × 2 fractions within one day. Median follow-up time was 4.4 years. RESULTS: Actuarial rates of no biochemical evidence of disease, overall survival and metastasis-free survival for all patients were 96%,98% and 98%, respectively. The cumulative incidence of acute grade 2 and 3 genitourinary (GU) toxicity was 9% and 2%, respectively. The corresponding incidences of late GU toxicity were 18% and 1%. No grade ≥4 of either type of toxicity was detected. Multivariate analysis showed that having higher international prostate symptom score (IPSS; P = 0.041) or higher V200 (P = 0.013) was associated with a higher risk of experiencing any grade of acute GU toxicity. In addition, patients having a higher IPSS (P = 0.019) or a higher V150 (P = 0.033) were associated with a higher grade >1 acute GU toxicity. CONCLUSIONS: The findings of this study show that HDR-BT 13.5 Gy × 2 as monotherapy was safe and effective for prostate cancer patients with low-intermediate risk.

Impact of treatment time and dose escalation on local control in locally advanced cervical cancer treated by chemoradiation and image-guided pulsed-dose rate adaptive brachytherapy.

PURPOSE: To report the prognostic factors for local control in patients treated for locally advanced cervical cancer with image guided pulsed-dose rate brachytherapy. MATERIALS/METHODS: Patients treated with curative intent by a combination of external beam radiotherapy and pulsed-dose rate brachytherapy were selected. Local failure was defined as any relapse in the cervix, vagina, parametria, or uterus during follow-up. Prognostic factors were selected based on log rank tests and then analyzed with a Cox model. Dose/effect correlations were performed using the probit model. RESULTS: Two hundred and twenty-five patients treated from 2006 to 2011 were included. According to the FIGO classification, 29% were stage IB, 58% stage II, 10% stage III, and 3% stage IVA; 95% received concomitant chemotherapy. Thirty patients were considered having incomplete response or local failure. Among the selected parameters, D90 for HR-CTV, D90 for IR-CTV, the overall treatment time, the TRAK, and the HR-CTV volume appeared significantly correlated with local control in univariate analysis. In multivariate analysis, overall treatment time >55days and HR-CTV volume >30cm(3) appeared as independent. The probit analysis showed significant correlations between the D90 for both CTVs, and the probability of achieving local control (p=0.008 and 0.024). The thresholds to reach to warrant a probability of 90% of local control were 85Gy to the D90 of the HR-CTV and 75Gy to 90% of the IR-CTV (in 2Gy equivalent, α/ß=10). To warrant the same local control rate, the D90 HR-CTV should be significantly increased in stage III-IV tumors, in case of HR-CTV >30cm(3), excessive treatment time, or tumor width at diagnosis >5cm (97, 92, 105, and 92Gy respectively). CONCLUSIONS: Overall treatment time and HR-CTV volume were independent prognostic factors for local control. The D90 for HR and IR CTV were significantly correlated with local control, and D90 HR-CTV should be adapted to clinical criteria.

Ethnic difference in risk of toxicity in prostate cancer patients treated with dynamic arc radiation therapy.

AIMS AND BACKGROUND: The objective of this study was to assess the influence of ethnicity on toxicity in patients treated with dynamic arc radiation therapy (ART) for prostate cancer (PC). METHODS: From June 2006 to May 2012, 162 cT1-T3 cN0 cM0 PC patients were treated with ART (primary diagnosis, n = 125; post-prostatectomy/brachytherapy biochemical recurrence, n = 26; adjuvant post-prostatectomy, n = 11) at 2 institutions. Forty-five patients were Latin Americans and 117 were Europeans. The dose prescribed to the prostate ranged between 68 Gy and 81 Gy. RESULTS: The median age was 69 years (range 43-87 years). The median follow-up was 18 months (range 2-74 months). Overall, only 3 patients died, none due to a cancer-related cause. Biochemical recurrence was seen in 7 patients. The rates of acute grade 2 gastrointestinal (GI) and genitourinary (GU) toxicities were 19.7% and 17%, respectively. Only 1 patient experienced acute grade 3 GI toxicity, whereas 11 patients (6.7%) experienced acute grade 3 GU toxicity. Multivariate analysis showed that undergoing whole pelvic lymph node irradiation was associated with a higher grade of acute GI toxicity (OR: 3.46; p = 0.003). In addition, older age was marginally associated with a higher grade of acute GI toxicity (OR: 2.10; p = 0.074). Finally, ethnicity was associated with acute GU toxicity: Europeans had lower-grade toxicity (OR: 0.27; p = 0.001). CONCLUSIONS: Our findings suggest an ethnic difference in GU toxicity for PC patients treated with ART. In addition, we found that ART is associated with a very low risk of severe toxicity and a low recurrence rate.

Pulsed-dose rate image-guided adaptive brachytherapy in cervical cancer: Dose-volume effect relationships for the rectum and bladder.

PURPOSE: To establish dose-volume effect correlations for late bladder and rectum side effects in patients treated for locally advanced cervical cancer with concomitant chemoradiation followed by pulsed-dose rate image-guided adaptive brachytherapy. MATERIAL AND METHODS: The dosimetric data, converted in 2 Gy equivalent, from 217 patients were confronted to late morbidity defined as any event lasting or occurring 90 days after treatment initiation. Toxicity was assessed using the CTC-AE 3.0. Probit analyses and Log rank tests were performed to assess relationships. RESULTS: One hundred and sixty-one urinary and 58 rectal events were reported, affecting 98 (45.1%) and 51 (23.5%) patients, respectively. Cumulative incidences for grade 2-4 bladder and rectal morbidity were 24.3% and 9.6% at 3 years, respectively. Significant relationships were observed between grade 2-4 and 3-4 events and D0.1cm(3) and D2 cm(3) for the bladder and between grade 1-4 and 2-4 event probability and rectal D2 cm(3). The effective doses for 10% grade 2-4 morbidity were 65.3 Gy (59.8-81.3), and 55.4 Gy (15.7-63.6), respectively, for the rectum and bladder. Without considering urinary and rectal incontinence, for which the pertinence of correlating them with D2 cm(3) is questionable, ED10 were 68.5 Gy (62.9-110.6) and 65.5 Gy (51.4-71.6 Gy). When sorting patients according to D2 cm(3) levels, patients with high D2 cm(3) had significantly lower morbidity free survival rates for grade 1-4 and 2-4 urinary and rectal morbidity. CONCLUSION: Significant dose-volume effect relationships were demonstrated between the modern dosimetric parameters and the occurrence of late rectal and urinary morbidity in patients treated with pulsed-dose-rate brachytherapy. Further studies are required to refine these relationships according to clinical cofactors, such as comorbidities.

Characterization and adequacy of the use of radiotherapy and its trend in time.

BACKGROUND AND PURPOSE: Characterization of radiotherapy activity and its trend over time. Gathering of parameters for future planning of our resources, applicable to similar population areas. Performing a clinical audit of appropriate use of radiotherapy. MATERIAL AND METHODS: Analysis of 9782 patients treated between 1998 and 2008. Descriptive statistics of pathologies and social/demographic characteristics. Intention of treatment. The rate of radiotherapy utilization was estimated and compared with those considered optimal. Rate of reirradiation. RESULTS: The average global rate of radiotherapy utilization for the period was 32.7%. It increased by 23% between 1998 and 2008, while the population of the area rose by 1.04%, equaling an average 1.13 irradiations/1000 inhabitants/year. Radiation treatment has increased by 13.6, 2.3, 1.6 and 1.06 times in patients with prostate, breast, rectal and lung cancer, respectively. Eight percent of radiotherapy treatments involve concurrent chemotherapy. The proportion of treatments with palliative intent was 18.2%. The overall underutilization of radiation therapy in our environment was an estimated 13.4%. CONCLUSIONS: The grade of adequacy of radiation rates in relation with scientific evidence was globally considered suboptimal, especially in lung cancer. There was an upward trend of irradiation in breast and prostate cancer, tending toward rates considered optimal.