Rectum and Bladder Toxicity in Postoperative Prostate Bed Irradiation: Dose-Volume Parameters Analysis.

Although prostate cancer treatment is increasingly effective, its toxicities pose a major concern. The aim of our study was to assess the rate of adverse events (AEs) and the prognostic value of dose-volume histogram (DVH) parameters for the occurrence of treatment toxicity in patients treated with post-prostatectomy prostate bed radiotherapy (RT). The AEs were scored according to the CTCAE v.5.0. The rectum and bladder were contoured according to the RTOG Guidelines. The DVH parameters were assessed using data exported from the ECLIPSE treatment-planning system. Genitourinary (GU) and gastrointestinal (GI) toxicity were analysed using consecutive dose thresholds for the percentage of an organ at risk (OAR) receiving a given dose and the QUANTEC dose constraints. A total of 213 patients were included in the final analysis. Acute grade 2 or higher (≥G2) GU AEs occurred in 18.7% and late in 21.3% of patients. Acute ≥G2 GI toxicity occurred in 11.7% and late ≥G2 in 11.2% of the patients. Five patients experienced grade 4 AEs. The most common adverse effects were diarrhoea, proctitis, cystitis, and dysuria. The most significant predictors of acute ≥G2 GI toxicity were rectum V47 and V46 (p < 0.001 and p < 0.001) and rectum wall V46 (p = 0.001), whereas the most significant predictors of late ≥G2 GI AEs were rectum wall V47 and V48 (p = 0.019 and p = 0.021). None of the bladder or bladder wall parameters was significantly associated with the risk of acute toxicity. The minimum doses to bladder wall (p = 0.004) and bladder (p = 0.005) were the most significant predictors of late ≥G2 GU toxicity. Postoperative radiotherapy is associated with a clinically relevant risk of AEs, which is associated with DVH parameters, and remains even in patients who fulfil commonly accepted dose constraints. Considering the lack of survival benefit of postoperative adjuvant RT, our results support delaying treatment through an early salvage approach to avoid or defer toxicity.

Artificial intelligence to predict outcomes of head and neck radiotherapy.

Head and neck radiotherapy induces important toxicity, and its efficacy and tolerance vary widely across patients. Advancements in radiotherapy delivery techniques, along with the increased quality and frequency of image guidance, offer a unique opportunity to individualize radiotherapy based on imaging biomarkers, with the aim of improving radiation efficacy while reducing its toxicity. Various artificial intelligence models integrating clinical data and radiomics have shown encouraging results for toxicity and cancer control outcomes prediction in head and neck cancer radiotherapy. Clinical implementation of these models could lead to individualized risk-based therapeutic decision making, but the reliability of the current studies is limited. Understanding, validating and expanding these models to larger multi-institutional data sets and testing them in the context of clinical trials is needed to ensure safe clinical implementation. This review summarizes the current state of the art of machine learning models for prediction of head and neck cancer radiotherapy outcomes.

Locally advanced NSCLC: a plea for sparing the ipsilateral normal lung-prospective, clinical trial with DART-bid (dose-differentiated accelerated radiation therapy, 1.8 Gy twice daily) by VMAT.

BACKGROUND: In radiation treatment of locally advanced non-small cell lung cancer (LA-NSCLC), 'margins' from internal target volumes to planning target volumes in the range of 12 to 23 mm are reported, and avoiding exposure of the contralateral lung is common practice. We investigated prospectively an approach with tight margins (7 mm) and maximal sparing of the ipsilateral normal lung. Mature results for the first endpoint (pneumonitis) and further toxicities are reported. METHODS: Primary tumors were treated by VMAT with 73.8-90.0 Gy in positive correlation to tumor volumes, nodes with 61.2 Gy, a restricted volume of nodes electively with 45 Gy. Fractional doses of 1.8 Gy bid, interval 8 h. Before radiotherapy, two cycles platin-based chemotherapy were given. 12 patients finished maintenance therapy with Durvalumab. Median follow up time for all patients is 19.4 months, for patients alive 27.0 months (3.4-66.5 months). RESULTS: 100 consecutive, unselected patients with LA-NSCLC in stages II through IVA were enrolled (UICC/AJCC, 8th edition). No acute grade 4/5 toxicity occurred. Pneumonitis grade 2 and 3 was observed in 12% and 2% of patients, respectively; lowering the risk of pneumonitis grade ≥ 2 in comparison to the largest study in the literature investigating pneumonitis in LA-NSCLC, is significant (p < 0.0006). Acute esophageal toxicity grade 1, 2 and 3 occurred in 12%, 57% and 3% of patients, respectively. Two patients showed late bronchial stricture/atelectasis grade 2. In two patients with lethal pulmonary haemorrhages a treatment correlation cannot be excluded. Median overall survival for all stage III patients, and for those with 'RTOG 0617 inclusion criteria' is 46.6 and 50.0 months, respectively. CONCLUSIONS: Overall toxicity is low. In comparison to results in the literature, maximal sparing the ipsilateral normal lung lowers the risk for pneumonitis significantly. TRIAL REGISTRATION: Ethics committee of Vorarlberg, Austria; EK-0.04-105, Registered 04/09/2017-Retrospectively registered. http://www.ethikkommission-vorarlberg.at.

Dose-volume predictors of post-radiation primary hypothyroidism in head and neck cancer: A systematic review.

BACKGROUND AND PURPOSE: This systematic review aims to identify radiation dose-volume predictors of primary hypothyroidism after radiotherapy in patients with head and neck cancer (HNC). MATERIALS AND METHODS: We performed a systematic literature search of Medline, EMBASE and Web of Science from database inception to July 1, 2021 for articles that discuss radiation dose-volume predictors of post-radiation primary hypothyroidism in patients with HNC. Data on the incidence, clinical risk factors and radiation dose-volume parameters were extracted. A meta-analysis was performed using the random-effects model to estimate the pooled odds ratio (OR) of thyroid volume as a predictor of the risk of post-radiation hypothyroidism, adjusted for thyroid radiation dosimetry. RESULTS: Our search identified 29 observational studies involving 4,530 patients. With median follow-up durations ranging from 1.0 to 5.3 years, the average crude incidence of post-radiation primary hypothyroidism was 41.4 % (range, 10 %-57 %). Multiple radiation dose-volume parameters were associated with post-radiation primary hypothyroidism, including the thyroid mean dose (Dmean), minimum dose, V25, V30, V35, V45, V50, V30-60, VS45 and VS60. Thyroid Dmean and V50 were the most frequently proposed dosimetric predictors. The pooled adjusted OR of thyroid volume on the risk of post-radiation primary hypothyroidism was 0.89 (95 % confidence interval, 0.85-0.93; p < 0.001) per 1 cc increment. CONCLUSION: Post-radiation primary hypothyroidism is a common late complication after radiotherapy for HNC. Minimizing inadvertent exposure of the thyroid gland to radiation is crucial to prevent this late complication. Radiation dose-volume constraints individualized for thyroid volume should be considered in HNC radiotherapy planning.

Adenoid cystic carcinoma of trachea: long-term disease control after endoscopic surgery and radiotherapy.

Aim: Adenoid cystic carcinoma is a rare tumor of head and neck region and its development in the thoracic region is even less frequent. This implies the absence of guidelines for therapeutic management and a consequent case-by-case approach. The role of radiotherapy is not yet clearly defined, but intensity-modulated radiotherapy allows for improved organ-at-risk sparing. Materials & methods: We have collected the cases of four patients treated at our institutions by the means of intensity-modulated radiotherapy, after endoscopic resection. Results & conclusion: Patients treated achieved long-term disease control of about 5 years, with a minimal acute toxicity. Longer follow-up is needed to drain conclusion on the impact of this treatment on overall survival.

Cardiac death after breast radiotherapy and the QUANTEC cardiac guidelines.

BACKGROUND: Breast/chest wall irradiation (RT) increases risk of cardiovascular death. International Quantitative Analysis of Normal Tissue Effects in the Clinic (QUANTEC) guidelines state for partial heart irradiation a "V25Gy <10% will be associated with a <1% probability of cardiac mortality" in long-term follow-up after RT. We assessed whether women treated with breast/chest wall RT 10-years ago who died of cardiovascular disease (CVD) violated QUANTEC guidelines. MATERIALS/METHODS: A population-based database identified all cardiovascular deaths in women with early-stage breast cancer <80 years, treated with adjuvant breast/chest wall RT from 2002 to 2006. Ten-year rate of cardiovascular death was calculated using a Kaplan-Meier method. Patients were matched on a 2:1 basis with controls that did not die of CVD. For left-sided cases, the heart and left anterior descending (LAD) artery were retrospectively delineated. Dose-volume histograms were calculated, and heart V25Gy compared to QUANTEC guidelines. RESULTS: 5249 eligible patients received breast/chest wall RT from 2002 to 2006: 76 (1.4% at 10-years) died of CVD by June 2015. Forty-two patients received left-sided RT (1.7% CVD death at 10-years), 34 right-sided RT (1.3% at 10-years). Heart V25Gy did not exceed 10% in any left-sided cases. No cardiac dosimetry parameter distinguished left-sided cases from controls. CONCLUSIONS: QUANTEC guidelines were not violated in any patient that died of CVD after left-sided RT. The risk of radiation induced cardiac death at 10-years appears to be very low if MHD is <3.3 Gy and maximum LAD dose (EQD23 Gy) is <45.4 Gy. Further studies are needed to evaluate heart and LAD constraints in the CT-planning era.

The role of parotid gland irradiation in the development of severe hyposalivation (xerostomia) after intensity-modulated radiation therapy for head and neck cancer: Temporal patterns, risk factors, and testing the QUANTEC guidelines.

BACKGROUND: The aims of this study were to investigate temporal patterns and potential risk factors for severe hyposalivation (xerostomia) after intensity-modulated radiotherapy (IMRT) for head and neck cancer (HNC), and to test the two QUANTEC (Quantitative Analysis of Normal Tissue Effects in the Clinic) guidelines. PATIENTS AND METHODS: Sixty-three patients treated at the Memorial Sloan Kettering Cancer Center between 2006 and 2015, who had a minimum of three stimulated whole mouth saliva flow measurements (WMSFM) at a median follow-up time of 11 (range: 3-24) months were included. Xerostomia was defined as WMSFM ≤25% compared to relative pre-radiotherapy. Patients were stratified into three follow-up groups: 1: <6 months; 2: 6-11 months; and 3: 12-24 months. Potential risk factors were investigated (Mann-Whitney U test), and relative risks (RRs) assessed for the two QUANTEC guidelines. RESULTS: The incidence of xerostomia was 27%, 14% and 17% at follow-up time points 1, 2 and 3, respectively. At <6 months, the mean dose to the contralateral and the ipsilateral parotid glands (Dmeancontra, Dmeanipsi) was higher among patients with xerostomia (Dmeancontra: 25 Gy vs. 15 Gy; Dmeanipsi: 44 Gy vs. 25 Gy). Patients with xerostomia had higher pre-RT WMSFM (3.5 g vs. 2.4 g), and had been treated more frequently with additional chemotherapy (93% vs. 63%; all 4 variables: p < 0.05). At 6-11 months, Dmeancontra among patients with xerostomia was higher compared to patients without (26 Gy vs. 20 Gy). The RR as specified by the one- and two-gland QUANTEC guideline was 2.3 and 1.4 for patients with <6 months follow-up time, and 2.0 and 1.2 for patients with longer follow-up (6-11 + 6-24 months). CONCLUSION: Xerostomia following IMRT peaks within six months post-radiotherapy and fades with time. Limiting the mean dose to both parotid glands (ipsilateral <25 Gy, contralateral <25 Gy) and reducing the use of chemotherapy will likely decrease the rate of xerostomia. Both QUANTEC guidelines are effective in preventing xerostomia.

Internal and external generalizability of temporal dose-response relationships for xerostomia following IMRT for head and neck cancer.

BACKGROUND AND PURPOSE: To study internal and external generalizability of temporal dose-response relationships for xerostomia after intensity-modulated radiotherapy (IMRT) for head and neck cancer, and to investigate potential amendments of the QUANTEC guidelines. MATERIAL AND METHODS: Objective xerostomia was assessed in 121 patients (nCohort1=55; nCohort2=66) treated to 70Gy@2Gy in 2006-2015. Univariate and multivariate analyses (UVA, MVA with 1000 bootstrap populations) were conducted in Cohort1, and generalizability of the best-performing MVA model was investigated in Cohort2 (performance: AUC, p-values, and Hosmer-Lemeshow p-values (pHL)). Ultimately and for clinical guidance, minimum mean dose thresholds to the contralateral and the ipsilateral parotid glands (Dmeancontra, Dmeanipsi) were estimated from the generated dose-response curves. RESULTS: The observed xerostomia rate was 38%/47% (3months) and 19%/23% (11-12months) in Cohort1/Cohort2. Risk of xerostomia at 3months increased for higher Dmeancontra and Dmeanipsi (Cohort1: 0.17·Dmeancontra+0.11·Dmeanipsi-8.13; AUC=0.90±0.05; p=0.0002±0.002; pHL=0.22±0.23; Cohort2: AUC=0.81; p<0.0001; pHL=0.27). The identified minimum Dmeancontra thresholds were lower than in the QUANTEC guidelines (Cohort1/Cohort2: Dmeancontra=12/19Gy; Dmeancontra, Dmeanipsi=16, 25/20, 26Gy). CONCLUSIONS: Increased Dmeancontra and Dmeanipsi explain short-term xerostomia following IMRT. Our results also suggest decreasing Dmeancontra to below 20Gy, while keeping Dmeanipsi to around 25Gy. Long-term xerostomia was less frequent, and no dose-response relationship was established for this follow-up time.

A Kindler syndrome-associated squamous cell carcinoma treated with radiotherapy.

Kindler syndrome1, 2 is a genetic disorder mainly characterized by increased skin fragility and photosensitivity,3, 4 making the use of treatments based on radiation difficult or even prohibited. Thus, cases reporting Kindler syndrome patients treated with radiotherapy are rare. In this study, we report clinical outcomes and care provided for a rare case of a Kindler syndrome patient submitted to radiotherapy. Diagnosed with squamous cell carcinoma involving the buccal mucosa, the patient was exclusively treated with radiotherapy, with 70 Gy delivered on the PTV with the Volumetric Modulated Arc technique. The patient's reaction regarding control of the lesion is relevant compared to patients not affected by the syndrome. We noticed acute reactions of the skin and buccal mucosa after few radiotherapy sessions, followed by a fast reduction in the tumor volume. The efficacy of radiotherapy along with multidisciplinary actions allowed treatment continuity, leading to a complete control of the lesion and life quality improvement and showed that the use of radiotherapy on Kindler syndrome patients is possible.

Xerostomia in patients treated for oropharyngeal carcinoma: comparing linear accelerator-based intensity-modulated radiation therapy with helical tomotherapy.

BACKGROUND: In comparison to sliding-window intensity-modulated radiation therapy (sw-IMRT), we hypothesized that helical tomotherapy (HT) would achieve similar locoregional control and, at the same time, decrease the parotid gland dose, thus leading to a xerostomia reduction. METHODS: The association between radiation techniques, mean parotid dose, and xerostomia incidence, was reviewed in 119 patients with advanced oropharyngeal carcinoma treated with concurrent chemoradiation using sw-IMRT (n = 59) or HT (n = 60). RESULTS: Ipsilateral and contralateral parotid mean doses were significantly lower for patients treated with HT versus sw-IMRT: 24 Gy versus 32 Gy ipsilaterally and 20 Gy versus 25 Gy contralaterally. The incidence of grade ≥2 xerostomia was significantly lower in the HT group than in the sw-IMRT group: 12% versus 78% at 6 months, 3% versus 51% at 12 months, and 0% versus 25% at 24 months. Total parotid mean dose <25 Gy was strongly associated to a lower incidence of grade ≥2 xerostomia at 6, 12, and 24 months. CONCLUSION: This retrospective series suggests that using HT can better spare the parotid glands while respecting quantitative analysis of normal tissue effects in the clinic (QUANTEC)'s criteria.

Evaluation of canal preparation for apical sealing with various Ni-Ti rotary instruments / 대한치과보존학회지

OBJECTIVES: The aim of this study was to evaluate the various NiTi rotary instruments regarding their ability to provide a circular apical preparation. MATERIALS AND METHODS: 50 single canal roots were selected, cut at the cementodentinal junction and the coronal 1/3 of the canals was flared using Gates Glidden burs. Samples were randomly divided into 5 experimental groups of 10 each. In group I, GT files, Profile 04 and Quantec #9 and #10 files were used. In Group II Lightspeed was used instead of Quantec. In Group III, Orifice shaper, Profile .06 series and Lightspeed were used. In Group IV, Quantec #9 and #10 files were used instead of Lightspeed. In Group V, the GT file and the Profile .04 series were used to prepare the entire canal length. All tooth samples were cut at 1 mm, 3 mm and 5 mm from the apex and were examined under the microscope. RESULTS: Groups II and III (Lightspeed) showed a more circular preparation in the apical 1mm samples than the groups that used Quantec (Group I & IV) or GT files and Profile .04 series.(Group V)(p < 0.05) There was no significant difference statistically among the apical 3, 5 mm samples. In 5 mm samples, most of the samples showed complete circularity and none of them showed irregular shape. CONCLUSIONS: Lightspeed showed circular preparation at apical 1 mm more frequently than other instruments used in this study. However only 35% of samples showed circularity even in the Lightspeed Group which were enlarged 3 ISO size from the initial apical binding file (IAF) size. So it must be considered that enlarging 3 ISO size isn't enough to make round preparation.

Avaliação do sistema Quantec SC usado nas velocidades de 350 ou 700rpm em retratamento endodôntico / Evaluation of Quantec SC instrument, using speed at 350 or 700rpm in endodontic retreatment

O objetivo deste estudo foi analisar a capacidade do sistema rotatório Quantec SC de remover guta-percha e/ou cimento de canais quando usado na velocidade de 350 ou 700rpm. Vinte incisivos inferiores extraídos foram obturados pela técnica da condensação lateral com guta-percha e cimento Ketac-Endo. Após seis meses as obturações foram removidas com o sistema rotatório Quantec SC na velocidade de 350 ou 700rpm. Inicialmente foram avaliados o tempo para a remoção da obturação, a extrusão de material obturador bem como o desvio do trajeto do canal, perfuração e a fratura de instrumento. A seguir os dentes foram seccionados longitudinalmente e a limpeza das paredes dos canais foi avaliada usando o software Sigma Scan. Aos dados obtidos foi aplicado o teste estatístico de Kruskal-Wallis. Observou-se que todos os canais exibiram resíduos de material obturador; a 700rpm o tempo de remoção da obturação foi menor, porém,a 350rpm menor quantidade de resíduos de guta-percha e cimento foram observadas. Quanto a extrusão de material obturador, não foram observadas diferenças estatísticas entre as velocidades de 350 e 700rpm. Fraturas de instrumento ocorreram em ambas as velocidades sendo mais frequentes no instrumento nº5; o número de perfurações e desvios do trajeto do canal foi maior na velocidade de 350rpm. Conclui-se que os instrumentos rotatórios do sistema Quantec SC podem ser utilizados para desobstrução de canais na velocidade de 700rpm.

The aim of this study was compare the ability of Quantec SC rotary system to remove gutta-percha and sealer from root canal when used using speed, 350 or 700rpm. Twelve extracted mandibular incisors were filled by lateral condensation with gutta-percha and Ketac-Endo sealer. After six months the root canal obturations were removed with Quantec SC rotary system, at speed of 350 or 700rpm. The teeth were grooved longitudinally and evaluated using the Sigma ScanII software. Were evaluated: time to gutta-percha removal, canal wall cleanliness and extruded material. The Kruskal- Wallis on-way analysis of variance was used to identify any significance differences amongst two groups. The number of canal transportation and fracture instruments was also recorded. All examined teeth had filling residues in the rootcanal; in 700rpm the time of work was reduced but at 350rpm more gutta-percha and cements was removed. Extruded material did not show difference at 350 or 700rpm. Procedures errors, instrument fractures occurred in both speed but most frequently in # 5 instrument; canal transportation and perforation occurred most in 350rpm. According to this studyQuantec SC system could be used at 700 rpm to root canal obsturation remotion.