Clinical oncology最新文献

Aim: Artificial intelligence (AI) based auto-segmentation aids radiation therapy (RT) workflows and is being adopted in clinical environments facilitated by the increased availability of commercial solutions for organs at risk (OARs). In addition, open-source imaging datasets support training for new auto-segmentation algorithms. Here, we studied if the female and male anatomies are equally represented among these solutions.

Materials and methods: Inquiries were sent to eight vendors regarding their clinically available OAR auto-segmentation solutions for each gender. The Cancer Imaging Archive (TCIA) was also screened for publicly available imaging datasets specific to the female and the male anatomy.

Results: All vendors provided AI based auto-segmentation solutions for the male pelvis and female breasts, while 5/8 vendors provided solutions for the female pelvis. The female breast and the female pelvis solutions were released at a median of 0.6 years and 2.3 years, respectively, after the release of the male pelvis solutions. Among 27 TCIA datasets identified, 15 involved the female anatomy (breast: 10; pelvis: 5) and 12 involved the male pelvis but no female-specific dataset included OAR segmentations, while three male pelvis datasets included OARs (ejaculatory duct, neurovascular bundle, penile bulb and verumontanum).

Conclusion: Commercial AI auto-segmentation solutions and open-source imaging datasets include considerably more solutions and OAR segmentations for male cancer over female cancer sites. This gender disparity is likely to propagate throughout the RT pipeline.

Aims: To assess the robustness of 4D-optimised IMPT and PAT plans against interplay effects in non-small cell lung cancer (NSCLC) patients with respiratory motion over 10 mm, and to provide insights into the use of proton-based stereotactic body radiotherapy (SBRT) for lung cancer with significant tumour movement.

Materials and methods: Fourteen patients with early-stage NSCLC and tumour motion >10 mm were selected. Three hypofraction regimens were generated using 4D robust optimisation with the IMPT and PAT techniques. The nominal plan qualities for both techniques were compared, and their robustness against setup and range uncertainties was evaluated. 4D dynamic dose and the 4D static dose were generated to calculate ΔI_M^R(%) for interplay effects.

Results: PAT plans demonstrated superior target metrics such as D₉₅ and D₂, and offered enhanced protection for organs at risk (OARs), particularly in lung metrics, across multiple fractionation schemes (p < 0.05). The robustness of target coverage against setup and range uncertainties was better in PAT plans than IMPT, with average pass rates of 97.8% and 95.4%, respectively (p < 0.01). The interplay effect significantly affected target metrics in single-fraction plans, decreasing with more fractions, while its effect on OAR metrics was minimal. Median values for single-fraction plans were: ΔI_D98^GTV was -3% for IMPT and -0.7% for PAT (p < 0.01); ΔI_D95^GTV was -2.4% for IMPT and -0.6% for PAT (p < 0.01); ΔI_D2^GTV was 3.2% for IMPT and 0.9% for PAT (p < 0.05). The interplay effects resulted in median homogeneity index deviations of 9.1% and 2% for the IMPT and PAT plans, respectively (p < 0.01). Different starting phases affected IMPT more significantly than PAT.

Conclusion: PAT demonstrated greater robustness to interplay effects than IMPT for hypofractionated treatments of early-stage NSCLC, particularly in single-fraction schemes. Additionally, PAT showed good resilience to variations in different starting phases.

Aims: The role of radiotherapy (RT) for inoperable gastric cancer (IGC) is commonly low-dose, given reactively for symptoms (e.g. bleeding), in contrast to the oesophagus, where high quality evidence exists for higher doses of RT. This systematic review aims to evaluate the use of, and evidence for, definitive and high-dose palliative RT for IGC and whether a change in practice is warranted.

Materials and methods: Following registration with PROSPERO (CRD42022297080), MEDLINE, EMBASE and The Cochrane Library were searched in accordance with PRISMA standards for studies evaluating definitive (non-metastatic disease, BED10 >45Gy) or high-dose palliative RT (for symptom/local control, minimum BED10 >30Gy). A manual search of meeting proceedings and clinical trial registries was also performed.

Results: 31 studies were selected for analysis. 10 definitive studies totalling n = 354 patients receiving RT with 45-50.4Gy/25-28#, showed median overall survival ranging between 11 and 26.4 months, clinical complete response range 12%-45%, G3 gastrointestinal toxicity 0-31% (range) and RT completion rates ranging from 81% to 100%. 21 high-dose palliative studies (n = 955) mostly evaluated haemostatic control and reported 38 different RT regimens (most commonly 30Gy/10#). Bleeding response rate (RR) was 59.6%-90%, pain RR 45.5-100%, obstruction RR 52.9%-100%, G3 gastrointestinal toxicity <5% and RT completion 68%-100%. An additional American National Cancer Database review >4700 non metastatic IGC patients which combined both definitive and palliative doses found significant benefit to RT in addition to chemotherapy. Evidence regarding a dose-response relationship is conflicting, limited by retrospective data. Two studies report high quality -of-life (QOL) scores following gastric RT.

Conclusion: There is a body of mainly non-randomised, observational evidence showing high-dose RT is efficacious, safe and may maintain QOL for patients with IGC. A change in practice will require a prospective randomised controlled trial, which should explore the role of prophylactic, high-BED RT combined with optimal systemic therapy using modern IMRT techniques and RT quality assurance.

Diffuse midline glioma (DMG) continues to be an aggressive brain stem cancer among children and young adults. It has a dismal prognosis, with less than 10% of patients alive two years after diagnosis. Radiotherapy has been demonstrated to be effective, albeit transient. Hence, radiotherapy is considered a cornerstone in the treatment. Reirradiation has, in retrospective studies, shown promising overall survival and palliative effect, but no pan-European consensus for reirradiation exists. The REMIT (Reirradiation of diffuse Midline glioma paTients) protocol evaluates safety and the palliative efficacy of reirradiation of patients with DMG (clinicaltrials.gov NCT06093165). Patients included in the protocol will be followed with 1) performance status (Karnofsky or Lansky), 2) toxicity monitored with Common Terminology Criteria for Adverse Events (CTCAE), 3) motor and functioning skill with PEDI-CAT (The Pediatric Evaluation of Disability Inventory) and 4) quantification of corticosteroid use. Furthermore, the impact on quality of life and well-being will be assessed qualitatively with interviews as well as with the Pediatric Quality of Life Inventory (PedsQl) Cancer Module questionnaire. The protocol also includes dose accumulation and contouring studies to assess standardization as well as a prescreening log to address selection bias of patients. The safety and palliative efficacy of reirradiation in DMG will be prospectively evaluated, including qualitative patient reported outcomes, through the REMIT protocol. REMIT is planned to open for inclusion in 2024.

Aims: Intracavitary brachytherapy alone covers a limited target volume; however, intracavitary and interstitial brachytherapy (IC/IS) can increase the dose coverage. We aim to assess the factors that impact D90 high-risk clinical target volume (HR-CTV) dose. We also assess clinical outcomes and toxicities for 3D image-based brachytherapy.

Materials and methods: We included a total of 424 cervical cancer patients with FIGO stage IB1 to IVA who received chemoradiation and high-dose-rate brachytherapy between 2014 and 2023. Target delineation was per GEC-ESTRO guidelines with the aim to achieve total dose of ≥85 Gy (D90 HR-CTV) in equivalent dose (EQD2). Implantation, tumour size, lateral extension, and HR-CTV volume were analysed.

Results: The median follow-up time was 24 months (range 1-107). The overall 2-year local control, progression-free survival, and overall survival rate were 90.3%, 75%, and 95.5%, respectively. Of 424 patients, 86.8% received a total dose of at least 85 Gy of D90 HR-CTV in EQD2. In multivariate analysis, IC/IS brachytherapy and HR-CTV volume were significant factors associated with HR-CTV D90 ≥ 85Gy in EQD2 (P = 0.012 and P = 0.000, respectively). Subgroup analysis of patients with HR-CTV volume >35 ml found that IC/IS was a significant factor in achieving HR-CTV D90 ≥ 85Gy in EQD2 (P = 0.017). At the median follow-up, patients with D90 HR-CTV ≥85 Gy achieved local control rates of 72.08% in small volume (<20 cm³) group, 68.42% in intermediate volume (21-30 cm³) group, 71.68% in high intermediate volume (31-60 cm³) and 17.67% in larger volume (>60 cm³) group (P = 0.005). Grade 3 toxicities including proctitis, cystitis, and vaginal stenosis were 7.1%, 1.9% and 0.2%, respectively.

Conclusion: IC/IS brachytherapy may be used in patients with HR-CTV volumes greater than 35 ml to achieve total doses of D90 HR-CTV ≥85 Gy in EQD2. IC/IS brachytherapy also provide good local control with favorable toxicity profile.

Aims: Neoadjuvant radiotherapy is an integral part of the management of locally advanced rectal cancer. Radiotherapy can be delivered using three-dimensional conformal radiotherapy (3DCRT) and intensity-modulated radiotherapy (IMRT) techniques. We herein compare the quality-of-life (QOL) outcomes of patients who received radiotherapy using these techniques in a randomised trial.

Materials and methods: A phase II randomised trial was conducted in patients with locally advanced rectal cancer. Patients staged as T3-4, N (any), or circumferential resection margin at risk were eligible. All patients underwent neoadjuvant chemoradiotherapy with 50.4 Gy given in 28 fractions with concomitant fluorouracil or capecitabine. Patients were randomly allocated, in a 1:1 ratio, to 3DCRT or IMRT planning techniques. QOL, a secondary objective of the study, was evaluated using the European Organisation for Research and Treatment for Cancer (EORTC) Quality of Life Questionnaire (QLQ) C30 and QLQ CR29 questionnaires at baseline, during the final week of radiotherapy and, at six months after radiotherapy. The impact of the treatment arm on QOL scores was evaluated using analysis of covariance after adjusting for the preintervention scores.

Results: 94 patients were accrued between October 2014 and March 2020. The trial was terminated early due to futility of the primary outcome, acute gastrointestinal toxicity, at interim analysis. Eighty-six (91%) patients completed the baseline questionnaire and one other timepoint of assessment. Median follow-up was 1.9 years. Overall, both during the final week of radiotherapy and at six months, emotional functioning had improved, but physical, role, and social functionings had declined compared to that at baseline. At baseline, there was no difference in QOL scores between the two arms. During the final week of radiotherapy, the IMRT arm was associated with better adjusted mean physical (p = 0.04) and role functioning (p = 0.01) scores.

Conclusion: IMRT is associated with limited QOL benefits compared to 3DCRT in patients undergoing neoadjuvant chemoradiotherapy for locally advanced rectal cancer.

Aims: While systemic management of high risk colon cancer is well addressed, advances in local management remain incremental. This study aims to identify a group of colon cancer patients where local management remains a challenge, and where intensifying local treatment with radiotherapy is potentially beneficial to minimise the risk of an R1 resection.

Materials and methods: The patients with select cT4 locally advanced primary colon (LAPC) (n = 40) and locally recurrent colon (LRC) (n = 48) adenocarcinomas who received neoadjuvant radiotherapy from 2005 to 2020 were studied. Radiotherapy prescription was 45-50.4 Gy in conventional fractionation. The estimated median follow-up time was 8.1 years and 6.3 years for the LAPC and LRC groups, respectively.

Results: The most common primary site was the sigmoid colon (n = 61). In the LAPC group, surgery was performed in 90% (n = 36), 81% (n = 29) of which were R0 resections, with pathologic downstaging occurring in 66.7% (n = 24). In the LRC group, surgery was possible in 79.2% (n = 38), 65.8% (n = 25) of which were R0 resections. For the LAPC group, 13% (n = 5) had local failures (hazard rate 3%, 95% CI 1-6%), 38% (n = 14) had any disease progression (hazard rate 9%; 95% CI 5-14), and 55% (n = 22) were alive at the end of the follow-up period (hazard rate 8%; 95% CI 5-13). For the LRC group, 35% (n = 17) had local failures (5-year local failure-free survival: 53%; 95% CI: 37-74), and 61% (n = 30) had any disease progression (5-year progression-free survival: 28%; 95% CI: 17%-48%). Five-year overall survival for the LRC group was 50% (95% CI: 37-68). There was no 30-day mortality.

Conclusion: Local management of high risk colon cancer remains a challenge. Future studies in neoadjuvant chemoradiation and systemic therapy, and staging methodology in identifying the high risk group are urgently needed.