Late Toxicity Research Articles

Response-adapted consolidation therapy strategy for patients with metastatic high-risk neuroblastoma: Results of the SMC NB-2014 study.

Tandem high-dose chemotherapy and autologous stem cell transplantation (HDCT/auto-SCT) and incorporation of 131I-metaiodobenzylguanidine (131I-MIBG) treatment have shown positive outcomes in high-risk neuroblastoma. However, more optimized treatment strategies are still needed. The NB-2014 study was a nonrandomized, prospective trial that examined survival outcomes in metastatic high-risk neuroblastoma patients using response-adapted consolidation therapy. We used post-induction residual 123I-MIBG status at metastatic sites as a treatment response marker. Patients achieving complete resolution of MIBG uptake at metastatic sites underwent a reduced first HDCT/auto-SCT with a 20% dose reduction in HDCT. After the first HDCT/auto-SCT, patients with remaining MIBG uptake received dose-escalated (18mCi/kg) 131I-MIBG treatment. In contrast, those with complete resolution of MIBG at metastatic sites received a standard dose (12mCi/kg) of 131I-MIBG. We compared survival and toxicity outcomes with a historical control group from the NB-2009. Of 65 patients treated, 63% achieved complete resolution of MIBG uptake at metastatic sites following induction chemotherapy, while 29% of patients still had MIBG uptake at metastatic sites after the first HDCT/auto-SCT. The 3-year event-free survival (EFS) and overall survival (OS) rates were 68.2%±6.0% and 86.5%±4.5%, respectively. Compared to NB-2009, EFS was similar (p=.855); however, NB-2014 had a higher OS (p=.031), a lower cumulative incidence of treatment-related mortality (p=.036), and fewer acute and late toxicities. Our results suggest that response-adaptive consolidation therapy based on chemotherapy response at metastatic sites facilitates better treatment tailoring, and appears promising for patients with metastatic high-risk neuroblastoma.

Spread-out Bragg peak FLASH: quantifying normal tissue toxicity in a murine model.

A favorable effect of ultra-high dose rate (FLASH) radiation on normal tissue-sparing has been indicated in several preclinical studies. In these studies, the adverse effects of radiation damage were reduced without compromising tumor control. Most studies of proton FLASH investigate these effects within the entrance of a proton beam. However, the real advantage of proton therapy lies in the Spread-out Bragg Peak (SOBP), which allows for giving a high dose to a target with a limited dose to healthy tissue at the entrance of the beam. Therefore, a clinically relevant investigation of the FLASH effect would be of healthy tissues within a SOBP. Our study quantified the tissue-sparing effect of FLASH radiation on acute and late toxicity within an SOBP in a murine model. Radiation-induced damage was assessed for acute and late toxicity in the same mice following irradiation with FLASH (Field dose rate of 60 Gy/s) or conventional (CONV, 0.34 Gy/s) dose rates. The right hindleg of unanesthetized female CDF1 mice was irradiated with single-fraction doses between 19.9-49.7 Gy for CONV and 30.4-65.9 Gy for FLASH with 5-8 mice per dose. The leg was placed in the middle of a 5 cm SOBP generated from a mono-energetic beam using a 2D range modulator. Acute skin toxicity quantified by hair loss, moist desquamation and toe separation was monitored daily within 29 days post-treatment. Late toxicity of fibrotic development measured by leg extendibility was monitored biweekly until 30 weeks post-treatment. Comparison of acute skin toxicity following radiation indicated a tissue-sparing effect of FLASH compared to conventional single-fraction radiation with a mean protection ratio of 1.40 (1.35-1.46). Fibrotic development similarly indicated normal tissue sparing with a 1.18 (1.17-1.18) protection ratio. The acute skin toxicity tissue sparing was similar to data from entrance-beam irradiations of Sørensen etal. (4). Full dose-response curves for acute and late toxicity after CONV and FLASH radiation were obtained. Radiation within the SOBP retains the normal-tissue-sparing effect of FLASH with a dose-modifying factor of 40% for acute skin damage and 18% for fibrotic development.

Impact of Dosimetric Compromises on Early Outcomes of Chordomas and Chondrosarcomas Treated With Image-guided Pencil Beam Scanning Proton Beam Therapy

PurposeTo critically review the clinical factors, dosimetry, and their correlation with early outcomes in patients with chordomas and chondrosarcomas treated with pencil beam scanning proton beam therapy (PBS-PBT). MethodsConsecutive 64 patients diagnosed with chordoma, or chondrosarcoma treated at our centre were studied. Patient, tumor and treatment-related factors including dosimetry were captured. Early and late toxicities and early outcomes were evaluated and correlated with clinical and dosimetric factors using standard statistical tools. ResultsThe median age of patients was 39(4-74 years) and most common site was skullbase (47%) followed by sacrum(31%) and mobile spine(22%). The median prescription dose to the high-risk CTV for chordoma and chondrosarcoma was 70.4CGE(Cobalt Gray equivalent) and 66CGE at 2.2CGE per fraction respectively. At presentation to our centre, 55% presented after a recurrence/progression of which 17% received prior radiation and 32% had a significant neural compression. At the time of PBT, 25% of patients had suboptimal neural separation. Three-fourths of patients had at least an acceptable target coverage. While 11% had a tier-1 compromise (GTVD98<90%), 14% had a tier-2 compromise (GTVD98<59CGE). With a median follow-up of 27.5 months, 2-year local control and PFS was 86.7% and 81.8% for chordomas and 87.5% and 77.1% for chondrosarcomas respectively. Residual GTV>25cc and a tier-2 compromise were associated with inferior local control (HR-0.19,p=0.019; HR-0.061,p=0.022 respectively) and progression-free survival (HR-0.128,p=0.014; HR-0.194,p=0.025 respectively) on multivariate analysis. Despite multiple surgeries, a majority with recurrent disease and prior radiations, grade-3 acute and late toxicities were limited and comparable to others in the literature. ConclusionDespite multiple surgeries, adequate neural separation was challenging to achieve. Severe dosimetric compromise(GTVD98<59CGE) led to inferior early outcomes. Adequate neural separation is key to avoiding dosimetric compromise and achieving optimal local control.

Bladder Tumor-Focused Adaptive Radiation Therapy: Clinical Outcomes of a Phase I Dose Escalation Study

Purpose/ObjectivesWe determine the maximum tolerated tumour focused dose (MTD) for the radical treatment of muscle invasive bladder cancer (MIBC) enabled by image guided adaptive radiotherapy (IGART) and long-term clinical outcomes. Materials/Methods: Fifty-nine patients with T2-T4aN0M0 unifocal urothelial MIBC suitable for daily radical radiotherapy were recruited prospectively to an ethics approved protocol (XX). The uninvolved bladder (PTVbladder) was planned to 52Gy in 32 fractions (f). The bladder tumour (PTVtumour) was planned to an assigned dose level of 68, 70, 72, or 74Gy. If organ at risk (OAR) dose constraints were violated, then PTVtumour was planned to 64Gy. Dose level allocation was determined by concurrent toxicity assessment of all previous patients recruited. Acute toxicity was evaluated using CTCAE v3.0; late toxicity was evaluated using RTOG criteria. The MTD was predefined as the highest dose level with estimated probability of ≤ 15% ≥G3 late toxicity and observed rate <50% acute G3 and <10% acute G4 toxicity. ResultsTwenty-six patients were assigned to 68Gy, of whom 6 were planned to 64Gy; 29 patients were assigned to 70Gy of whom 1 was planned to 68Gy, 2 patients were assigned and planned to 72Gy; no patients were assigned to 74Gy. Three patients did not complete treatment as planned, of whom only 1 patient stopped treatment because dose limiting toxicity occurred. The MTD was 70Gy. Acute genitourinary (GU) and gastrointestinal (GI) G3 acute toxicity was seen in 19% and 7% patients respectively. No grade 4 GU or GI toxicity was seen. Late toxicity (any) G3 and G4 was seen in 14% and 2% patients respectively. The 5-year overall survival was 58% (95% CI 44-71%). The bladder preservation rate was 89% (95% CI, 88 to 96%) with 6 patients not retaining native bladder function. ConclusionBladder tumour focused dose escalation to 70Gy using IGART is feasible with acceptable toxicity. This dose level has been evaluated in a phase II randomised control trial (XXXXX).

Helical Tomotherapy Versus 3-Dimensional Conformal Radiation Therapy in High-Risk Prostate Cancer: A Phase 3 Randomized Controlled Trial

We present long-term outcomes from a phase 3 randomized controlled trial that compared helical tomotherapy with 3-dimensional conformal radiation therapy (3D-CRT) in the treatment of high-risk prostate cancer. Newly diagnosed patients with high-risk prostate cancer were randomly allocated to receive radical radiation therapy (RT) using 3D-CRT or helical tomotherapy. In both arms, patients received an initial dose of 46 Gy in 23 fractions to the prostate and pelvic lymph nodes, followed by an additional boost to the prostate of 32 Gy in 16 fractions. RT was combined with 3 years of adjuvant androgen deprivation. The primary endpoint was late (>90 days since RT initiation) rectal toxicity. Overall,123 patients were randomly assigned to either the 3D-CRT (n = 60) or tomotherapy (n = 63) arms. The median follow-up was 161 months. Overall, the proportion of patients with grade ≥ 2 late rectal toxicity was 8.3% (95% CI, 3.1-19.1; n = 5) in the 3D-CRT arm and 11.1% (95% CI, 5.0-22.2; n = 7) in the tomotherapy arm with no significant between-arm difference (P = .83). There was no significant difference (P = .17) in the proportion of patients with late grade ≥ 2 genitourinary toxicity:10.0% (95% CI, 4.1-21.2) in the 3D-CRT arm and 20.6% (95% CI, 11.9-33.0) in the tomotherapy arm. There was no significant difference in the hazard of biochemical progression or death between the 2 groups (hazard ratio for the tomotherapy arm: 0.72; 95% CI, 0.46-1.15; P = .17). In this phase 3 trial, the overall incidence of grade ≥ 2 rectal toxicity was low and was not significantly different between the 2 arms. There was no significant evidence of improved biochemical progression-free survival in patients treated with tomotherapy. These findings should be interpreted considering the possibility of type II errors due to limited sample size and low event rates.

The role of radiotherapy in multimodal treatment of non-rhabdomyosarcoma soft tissue sarcomas in children: A real life report from a tertiary center.

The current treatment of pediatric non-rhabdomyosarcoma soft tissue sarcomas (NRSTS) is a multimodal risk-based approach. Today, smaller fields and lower doses of radiotherapy (RT) have become standard. In this study, it was aimed to evaluate the treatment outcomes and toxicity profile in children with NRSTS that received RT as a part of multimodal therapy. Twenty-nine patients with pediatric NRSTS treated with neoadjuvant or adjuvant RT between 1998 and 2022 were evaluated retrospectively. Kaplan-Meier method was used for survival analyses. Median follow-up was 36 months (range, 6-291 months). The median neoadjuvant and adjuvant RT doses were 50 Gy (range, 45-66 Gy) and 54 Gy (45-66 Gy), respectively. During follow-up, six (21%) patients developed a local recurrence and 10 (35%) had distant metastasis. The 5-year local control, overall survival (OS), local recurrence-free survival, and distant metastasis-free survival rate was 79%, 67%, 59%, and 61%, respectively. In multivariate analysis, a ≤5-cm tumor, gross tumor resection, Children's Oncology Group (COG) low-risk group, and absence of neoadjuvant chemotherapy were independent favorable prognostic factors for OS. Severe (≥ grade 3) late toxicity was observed in 6 (20%) patients. RT is a crucial component in the multimodal risk-based treatment approach for pediatric NRSTS. However, late toxicity rates are still high and should be improved. Patients with a ≤5-cm tumor, COG low-risk group and treated with gross tumor resection have increased survival rates.

Accelerated Radiotherapy Alone Versus Chemoradiation in Locally Advanced Carcinoma Cervix: Long-Term Outcomes.

Introduction Chemoradiation (CRT) is the standard of care for the treatment of carcinomacervix, more benefits of CRT are seen in the early stageas compared to a locally advanced stage. Altered fractionation such as accelerated radiotherapy (ART) in locally advanced carcinoma cervix has not been explored much. Here, we have reported the long-term outcome of ART in comparison to conventional CRT in locally advanced cervical cancer patients. Methods From September 2011 to January 2014, 191 patients with locally advanced squamous cell carcinoma of the uterine cervix, FIGO stage IIB - IIIB were included in this study. They were randomized into two arms: the CRTarm (95 patients) versus the ART arm (96 patients). During external beam radiotherapy (EBRT), the patients in the CRT arm received conventional radiotherapy 50 Gy/25 fractions, 2 Gy/fraction, 5 fractions/week with cisplatin 40 mg/m2/week while patients in the ART arm received 50 Gy/25 fractions, 2 Gy/fraction, 6 fractions per week (Monday to Saturday) radiation alone. This was followed by three insertions of 6.5 Gy per fraction of high dose rate (HDR) brachytherapy at one-week intervals in both arms to keep the total treatment time 50 days in the CRT arm versus 45 days in the ART arm. Results The median follow-up of the study population was 57 months (range: 4-108 months). The patients with no residual disease (NRD) after EBRT and complete response (CR) at first follow-up were statistically less in the ART arm as compared to the CRT arm (30.2% versus 53.7% and 42.7% versus 63.2%; p = 0.006 and p = 0.024, respectively). However, there was no statistical difference in response at six months. High-grade acute toxicities hematological (9.5%) and gastrointestinal (15.8%) were more prevalent in the CRT arm in comparison to the ART arm, with no statistical significance (p>0.05) and Grade 1/2 genitourinary toxicity was significantly higher in the CRT arm. Late toxicities in both groups were equivalent. Recurrence, distant type of recurrence, and time to recurrence were similar in both groups. Five-year rates of overall survival (OS) and disease-free survival (DFS) were 51.2% versus 37.2% (p = 0.087) and 57.1% versus 46.3% (p = 0.223) in the CRT arm versus ART arm, respectively. Conclusion ART is a compelling alternative to concurrent chemoradiotherapy for locally advanced cervical cancer, particularly in patients with significant comorbidities, elderly women, and those in higher stages where concurrent chemotherapy's efficacy diminishes. It should be strongly considered when chemotherapy is contraindicated.

X-Ray-Sensitizers: Organic Pharmaceutical Drug Intermediates Activated Directly by X-Rays to Efficiently Populate Triplet Excitons for Cancer Treatment

Radiotherapy is an important treatment for cancer, but it is associated with major side effects due to the high dose of radiation (generally more than 50 Gy). Because radiation’s low acute and late toxicity, many tumors are treated with fractionated radiation in small doses (< 2 Gy). Scintillator X-ray-induced photodynamic therapy is an efficient methodology for cancer management that employs small doses of X-ray irradiation (< 2 Gy) in a complex process. Here we screened pharmaceutical drug intermediates that are derivatives of thioxanthone (TX) and investigated TX-derived organic pharmaceutical molecules that efficiently undergo X-ray-sensitization to populate triplet excitons (singlet oxygen) for cancer therapy when exposed to low-dose X-ray irradiation. By modifying alkoxy side chain substitutions at the 2-position to tune the molecular packing and intermolecular interactions, the fluorescence and room-temperature phosphorescence of a series of TX derivatives were assessed under X-ray irradiation. The ability of these derivatives to generate singlet oxygen and their potential for treating tumors provide new opportunities for developing organic molecules with simple chemical structures, in which large numbers of triplets can be populated directly under ultralow-dose X-ray irradiation.

The spectrum of late radiation sequelae in head and neck cancer.

Concurrent Chemoradiation is the standard of care in the treatment of unresectable locally advanced head and neck cancer. Some of the acute side effects seen after or alongside the head and neck radiotherapy include dermatitis, mucositis, xerostomia, dysphagia and swallowing dysfunction. Evolving data demonstrate that acute toxicities may persist long-term and develop into late effects. In addition, late effects may manifest months or years after completion of therapy, persisting for years or even lifelong, far longer than previously believed. When severe, late effects may profoundly affect function and quality of life. The present study was conducted to analyze the spectrum of late radiation toxicities in head and neck cancer patients treated with radical external beam radiation therapy and to determine its prevalence and severity. This prospective observational study was conducted in the Department of Radiotherapy, Christian Medical College and Hospital, Ludhiana. In all patients with a histopathological diagnosis of head and neck carcinoma who have received radical radiation therapy alone or definitive chemoradiation as part of cancer-directed therapy. Salivary gland toxicity was the most common toxicity encountered in head and neck cancer survivors resulting in dysphagia followed by dental caries, subcutaneous late effects and dysphagia. As expected, the spectrum of side effects correlated with the primary site, stage of disease and ECOG performance status. Technological advancement in radiation planning and equipment has resulted in a reduction in the most feared side effects of radiation which has led to improvement in the quality of life of the survivors. As no technology can entirely protect normal tissues from irradiation, utmost care should be taken to minimize the radiation dose received by normal tissues by following preventive and supportive measures.

Efficacy and safety of low-dose celecoxib with chemoradiation in locally advanced head-and-neck squamous cell carcinoma

Background: Head-and-neck squamous cell carcinoma (HNSCC) is a major cancer in India with a poor prognosis. Novel antineoplastic agents, such as selective cyclooxygenase-2 inhibitors such as celecoxib, have shown antitumor, anti-angiogenesis, and radiosensitizing effects, improving radiotherapy response in many cancers. Aims and Objectives: This study aimed to determine the efficacy and safety of low-dose celecoxib combined with concurrent chemoradiation in Locally Advanced HNSCC. Materials and Methods: A double-arm prospective randomized control study was conducted, in which 103 eligible locally advanced HNSCC patients were randomized to concurrent chemoradiotherapy 66 Gy/2 Gy/33 fractions/61/2 weeks along with Inj Cisplatin 40 mg/m2 weekly either with celecoxib 100 mg twice daily (Study Arm – 62) or placebo (Control Arm – 41). Tumor response was evaluated using response evaluation criteria in solid tumors criteria 1.1 and acute toxicities based on the radiation therapy oncology group and common terminology criteria for adverse events criteria 5.0. Results: On analysis using the Chi-square test, the complete response rate was 65.6% in the study arm compared to 44.7% in the control arm, with P=0.0441 (significant at P&lt;0.05). The incidence of acute dermatitis and mucositis (grade ≥3) in the study and control arms was 29.3% versus 23.6%, with P=0.544 and 40% versus 37% with a P=0.782 (insignificant at P&lt;0.05), respectively. The patients in both arms were followed up to assess late toxicities, locoregional control rate, disease-free survival, and overall survival. Conclusion: Adding low-dose daily celecoxib to concurrent chemoradiation with weekly cisplatin in locally advanced HNSCC significantly improved the clinical response rates with acceptable treatment-related toxicities.

Re-re-irradiation for palliation: knowns, unknowns, and next steps.

With improving rates of survival among patients with metastatic malignancies, the request for palliative re-irradiation and re-re-irradiation continues to grow despite an absence of standardized guidelines. With only limited data regarding extra-cranial third-course palliative radiation, many radiation oncologists may feel uncomfortable proceeding with third-course irradiation of the same site. The review explores the available modern data regarding re-re-irradiation. A literature review identified four modern peer-reviewed studies investigating palliative, extra-cranial third-course irradiation with external beam radiation. These studies were retrospective, small, and heterogenous. While they reported comparable rates of pain palliation to first course irradiation and low rates of acute toxicity, interpretation is complicated by heterogeneous treatment parameters and insufficient reporting of cumulative dose equivalents and time intervals. With limited data available, it is critical to prioritize patient safety and quality of life in palliative radiotherapy. Patient selection should be meticulous, considering factors such as initial treatment response and predicted life expectancy. Conformal radiation techniques, strict immobilization, and daily image guidance should be employed to minimize toxicity to organs at risk (OARs). Long-term follow-up is essential for identifying and managing late toxicities effectively. Despite the scarcity of data, retrospective series suggest that extra-cranial third course irradiation can provide effective pain palliation comparable to first-course irradiation with tolerable rates of toxicity. However, careful consideration of patient prognosis and adherence to established principles of palliative radiotherapy are essential in decision-making. Further research and long-term follow-up are needed to refine treatment strategies and ensure safe and efficacious care delivery in this complex clinical scenario.

Intensity Modulated Carbon Ion Radiation Therapy Using Pencil Beam Scanning Technology for Patients With Unresectable Sacrococcygeal Chordoma

ObjectivesTo investigate the safety and efficacy of intensity modulated carbon ion radiotherapy (IM-CIRT) using pencil beam scanning technology for patients with unresectable sacrococcygeal chordoma (SC). Methods and MaterialsA total of 35 unresectable SC patients were retrospectively analyzed, including 54.3% (19/35) recurrent cases. 68.6% (24/35) cases’ tumor located in S2 or above, and all cases were treated with hypofractionated IM-CIRT. The median dose was 70.4 (range 69 - 80) Gy (RBE) in 16 (range 16 - 23) fractions, typically delivered over 5 fractions per week. ResultsThe 3-year OS, CSS, PFS, LRFS and DMFS rates with a median follow-up time of 42 (12∼91) months for the entire cohort were 93.2%, 96.3%, 61.8%, 80% and 77.3%, respectively. Multivariate analysis revealed that GTV volume (HR, 3.807; 95% CI: 1.044 - 13.887, p = 0.043) was the only significant prognostic factor for PFS and the dose for the GTV ≥ 70.4 Gy (RBE) was relevant with significantly better LRFS (HR, 0.190; 95% CI: 0.038 – 0.940, p = 0.042). No significant prognostic factor for OS, CSS and DMFS and no severe (i.e., grade ≥ 3) acute toxicity were identified. Severe late toxicities occurred in 3 patients (8.57 %): pain (1 patient), motor neuropathy (1 patient) and skin ulcer (1 patient). Furthermore, no severe toxicity related to urinary function or defecation was observed following IM-CIRT. Pain grades improved or remained unchanged in 85.7% of patients. ConclusionIM-CIRT produced acceptable 3-year outcomes without substantial late adverse effects, especially urinary and anorectal complications for SC, and did not appear to increase pain. IM-CIRT at high doses using hypofractionated RT may improve outcomes for local control and seems to be feasible even for postoperative recurrent SC.

A single-center experience of the upright proton therapy for skull-base chordomas and chondrosarcomas: Updated results

AimTo access efficacy and safety of the upright proton therapy for the skull-base chordomas and chondrosarcomas. Materials and methodsThe study encompasses single-center experience of proton therapy in chordomas (CA) and chondrosarcomas (CSA) of skull-base localization. We evaluate overall survival, local control and toxicity. Tumor response was assessed in accordance with RANO criteria. Treatment-related toxicity was evaluated with the help of CTCAE v 5.0 scale. ResultsProton therapy in the upright position was utilized for 51pts (patients) with CA-CSA (40 pts with chordoma and 11pts with chondrosarcoma) at the A. Tsyb Medical Radiological Research Center in 2016–2023. Median tumor volume constituted 30 cm3 (IQR (interquartile range) 15–41 cm3). Median total dose was 70 GyRBE. Median number of fractions was 35. Overall survival (OS) at 1-, 2- and 3-year rates reached 98.0 %, 88.6 % and 82.7 %, respectively. Median follow-up time was 36 months. The 1-, 2- and 3-year local control (LC) rates constituted, respectively, 98 %, 78.6 % and 66.3 %. Prior surgery showed statistically significant association with better prognosis (p = 0.023). Brainstem-to-tumor dose coverage compromise became the major pattern of LC failure (p = 0.03). The late radiation toxicity reactions included temporal lobe necrosis grade 2 in 2 pts, xerostomia grade 1 in 1pt, radiation cataract grade 2 in 1pt and persistent headache grade 2 in 4 pts. Severe late toxicity reactions were observed in 2 cases (4 %): 1 myelitis grade 3 and brainstem damage grade 5 in 1pt. ConclusionLocal control was achieved in the majority of patients receiving the scanning-beam upright proton therapy for skull-base CA-CSA. The LC rates after a surgery-radiotherapy combination treatment were higher compared with irradiation alone. Pattern of failure is mostly brainstem-tumor dose compromise. The high OS and LC rates were accompanied by low toxicity incidence. Even in complex case of the skull base CA-CSA upright proton therapy shows promising clinical outcomes.

Adjuvant Treatment of Stage I-II Serous Endometrial Cancer: A Single Institution 20-Year Experience.

Background: Serous endometrial carcinoma (SEC) is a high-risk subtype of endometrial cancer. The effectiveness of multiple adjuvant therapies, namely chemotherapy (CT), radiotherapy (RT), and sequential/concurrent chemotherapy with radiotherapy (CRT), have previously been investigated. However, optimal management of early-stage SEC remains unclarified. Methods: All cases of early-stage SEC (FIGO 2009 stages I-II) treated in our institution from 2002 to 2019 were identified. Patient data were documented until September 2023. Overall survival (OS) and disease-free survival (DFS) were computed using Kaplan-Meier estimates and Cox's proportional hazard model; descriptive statistical analysis was performed. Results: A total of 50 patients underwent total hysterectomy-bilateral salpingo-oophorectomy and omentectomy, displaying stage IA (60%), IB (24%), and II (16%) disease. The median follow-up was 90.9 months. Patients underwent adjuvant CRT (n = 36, 72%), CT (n = 6, 12%), or RT (n = 6, 12%). Two patients were observed and excluded from analyses. The 42 patients who received radiotherapy had pelvic external beam radiotherapy (n = 10), vaginal brachytherapy (n = 21), or both (n = 11). CRT had better OS (HR 0.14, 95%CI 0.04-0.52, p < 0.005) and DFS (HR 0.25, 95%CI 0.07-0.97, p = 0.05) than CT alone. RT displayed no OS or DFS benefits compared to CT/CRT. Recurrences were mostly distant. Acute and late G3-4 toxicities were primarily hematologic. Conclusions: Our data underline the challenge of treating SEC. CRT appears to be superior to CT alone but not to RT. Most recurrences were distant, highlighting the need for optimized systemic treatment options.

The Current Position of Postoperative Radiotherapy for Salivary Gland Cancer: A Systematic Review and Meta-Analysis.

Because of the rarity, heterogeneous histology, and diverse anatomical sites of salivary gland cancer (SGC), there are a limited number of clinical studies on its management. This study reports the cumulative evidence of postoperative radiotherapy (PORT) for SGC of the head and neck. A systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We searched the PubMed, Embase, Cochrane Library, and Web of Science databases between 7th and 10th November 2023. A total of 2962 patients from 26 studies between 2007 and 2023 were included in this meta-analysis. The median RT dose was 64 Gy (range: 56-66 Gy). The median proportions of high-grade, pathological tumor stage 3 or 4 and pathological lymph node involvement were 42% (0-100%), 40% (0-77%), and 31% (0-75%). The pooled locoregional control rates at 3, 5, and 10 years were 92% (95% confidence interval [CI], 89-94%), 89% (95% CI, 86-93%), and 84% (95% CI, 73-92%), respectively. The pooled disease-free survival (DFS) rates at 3, 5, and 10 years were 77% (95% CI, 70-83%), 67% (95% CI, 60-74%), and 61% (95% CI, 55-67%), respectively. The pooled overall survival rates at 3, 5, and 10 years were 84% (95% CI, 79-88%), 75% (95% CI, 72-79%), and 68% (95% CI, 62-74%), respectively. Severe late toxicity ≥ grade 3 occurred in 7% (95% CI, 3-14%). PORT showed favorable long-term efficacy and safety in SGC, especially for patients with high-grade histology. Considering that DFS continued to decrease, further clinical trials exploring treatment intensification are warranted.

Utilization of machine learning methods for prediction of acute and late rectal toxicity due to curative prostate radiotherapy.

Rectal toxicity is one of the primary dose-limiting side effects of prostate cancer radiotherapy, and consequential impairment on quality of life in these patients with long survival is an important problem. In this study, we aimed to evaluate the possibility of predicting rectal toxicity with artificial intelligence model which was including certain dosimetric parameters. One hundred and thirty-seven patients with a diagnosis of prostate cancer who received curative radiotherapy for prostate +/- pelvic lymphatics were included in the study. The association of the clinical data and dosimetric data between early and late rectal toxicity reported during follow-up was evaluated. The sample size was increased to 274 patients by synthetic data generation method. To determine suitable models, 15 models were studied with machine learning algorithms using Python 2.3, Pycaret library. Random forest classifier was used with to detect active variables. The area under the curve and accuracy were found to be 0.89-0.97 and 95%-99%, respectively, with machine learning algorithms. The sensitivity values for acute and toxicity were found to be 0.95 and 0.99, respectively. Early or late rectal toxicity can be predicted with a high probability via dosimetric and physical data and machine learning algorithms of patients who underwent prostate +/- pelvic radiotherapy. The fact that rectal toxicity can be predicted before treatment, which may result in limiting the dose and duration of treatment, makes us think that artificial intelligence can enter our daily practice in a short time in this sense.

Hypofractionated radiation therapy combined with androgen deprivation therapy for clinically node-positive prostate cancer.

This study aimed to analyze the treatment outcomes of combined definitive radiation therapy (RT) and androgen deprivation therapy (ADT) for clinically node-positive prostate cancer. Medical records of 60 patients with clinically suspected metastatic lymph nodes on radiological examination were retrospectively analyzed. Eight patients (13.3%) were suspected to have metastatic common iliac or para-aortic lymph nodes. All patients underwent definitive RT with a dose fractionation of 70 Gy in 28 fractions. ADT was initiated 2-3 months before RT and continued for at least 2 years. Biochemical failure rate (BFR), clinical failure rate (CFR), overall survival (OS), and prostate cancer-specific survival (PCSS) were calculated, and genitourinary and gastrointestinal adverse events were recorded. The median follow-up period was 5.47 years. The 5-year BFR, CFR, OS, and PCSS rates were 19.1%, 11.3%, 89.0%, and 98.2%, respectively. The median duration of ADT was 2.30 years. BFR and CFR increased after 3 years, and 11 out of 14 biochemical failures occurred after the cessation of ADT. Grade 2 and beyond late genitourinary and gastrointestinal toxicity rates were 5.0% and 13.3%, respectively. However, only two grade 3 adverse events were reported, and no grade 4-5 adverse events were reported. Patients with non-regional lymph node metastases did not have worse BFR, CFR, or adverse event rates. This study reported the efficacy and tolerable toxicity of hypofractionated definitive RT combined with ADT for clinically node-positive prostate cancer. Additionally, selected patients with adjacent non-regional lymph node metastases might be able to undergo definitive RT combined with ADT.

Proton therapy for intracranial meningioma: a single-institution retrospective analysis of efficacy, survival and toxicity outcomes.

To report the outcomes of a large series of intracranial meningiomas (IMs) submitted to proton therapy (PT) with curative intent. We conducted a retrospective analysis on all consecutive IM patients treated between 2014 and 2021. The median PT prescription dose was 55.8Gy relative biological effectiveness (RBE) and 66 GyRBE for benign/radiologically diagnosed and atypical/anaplastic IMs, respectively. Local recurrence-free survival (LRFS), distant recurrence-free survival (DRFS), overall survival (OS), and radionecrosis-free survival (RNFS) were evaluated with the Kaplan-Meier method. Univariable analysis was performed to identify potential prognostic factors for clinical outcomes. Toxicity was reported according to the latest Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Overall, 167 patients were included. With a median follow-up of 41 months (range, 6-99), twelve patients (7%) developed tumor local recurrence after a median time of 39 months. The 5-year LRFS was 88% for the entire cohort, with a significant difference between benign/radiologically diagnosed and atypical/anaplastic IMs (98% vs. 47%, p < 0.001); this significant difference was maintained also for the 5-year OS and the 5-year DRFS rates. Patients aged ≤ 56 years reported significantly better outcomes, whereas lower prescription doses and skull base location were associated with better RNFS rates. Two patients experienced G3 acute toxicities (1.2%), and three patients G3 late toxicities (1.8%). There were no G4-G5 adverse events. PT proved to be effective with an acceptable toxicity profile. To the best of our knowledge this is one of the largest series including IM patients submitted to PT.

Extended Follow-Up Outcomes from Pooled Prospective Studies Evaluating Efficacy of Interstitial Alpha Radionuclide Treatment for Skin and Head and Neck Cancers.

The initial favorable efficacy and safety profile for Alpha DaRT have been demonstrated (NCT04377360); however, the longer-term safety and durability of the treatment are unknown. This pooled analysis of four prospective trials evaluated the long-term safety and efficacy of Alpha DaRT for the treatment of head and neck or skin tumors. A total of 81 lesions in 71 patients were treated across six international institutions, with a median follow-up of 14.1 months (range: 2-51 months). Alpha DaRT sources were delivered via a percutaneous interstitial technique and placed to irradiate the tumor volume with the margin. The sources were removed two to three weeks following implantation. A complete response was observed in 89% of treated lesions (n = 72) and a partial response in 10% (n = 8). The two-year actuarial local recurrence-free survival was 77% [95% CI 63-87]. Variables, including recurrent versus non-recurrent lesions, baseline tumor size, or histology, did not impact long-term outcomes. Twenty-seven percent of patients developed related acute grade 2 or higher toxicities, which resolved with conservative measures. No grade 2 or higher late toxicities were observed. These data support the favorable safety profile of Alpha DaRT, which is currently being explored in a pivotal US trial.

Salvage low-dose-rate brachytherapy for locally recurrent prostate cancer after definitive irradiation

PurposeThe optimal management of locally recurrent prostate cancer after definitive irradiation is still unclear but local salvage treatments are gaining interest. A retrospective, single-institution analysis of clinical outcomes and treatment-related toxicity after salvage I-125 low-dose-rate (LDR) brachytherapy (BT) for locally-recurrent prostate cancer was conducted in a Comprehensive Cancer Center. Patients and methodsA total of 94 patients treated with salvage LDR-BT between 2006 and 2021 were included. The target volume was either the whole-gland +/- a boost on the GTV, the hemigland, or only the GTV. The prescribed dose ranged from 90 to 145 Gy. Toxicity was graded by Common Terminology Criteria for Adverse Events (CTCAE) v5.0. ResultsMedian follow-up was 34 months. Initial radiotherapy was external beam radiotherapy in 73 patients (78 %) with a median dose of 76 Gy and I-125 BT in 21 patients (22 %) with a prescribed dose of 145 Gy. Median PSA at salvage was 3.75 ng/ml with a median interval between first and salvage irradiation of 9.4 years. Salvage brachytherapy was associated with androgen deprivation therapy for 32 % of the patients. Only 4 % of the patients were castrate-resistant. Failure free survival was 82 % at 2 years and 66 % at 3 years. The only factors associated with failure-free survival on multivariate analysis were hormonosensitivity at relapse and European Association of Urology (EAU) prognostic group. Late grade 3 urinary and rectal toxicities occurred in 12 % and 1 % of the patients respectively.No significant difference in toxicity or efficacy was observed between the three implant volume groups. ConclusionThe efficacy and toxicity results are consistent with those in the LDR group of the MASTER meta-analysis. Salvage BT confirms to be an effective and safe option for locally recurrent prostate cancer. A focal approach could be interesting to reduce late severe toxicities, especially urinary.