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1.
Minerva Surg ; 79(4): 470-480, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38953759

ABSTRACT

Locally advanced extraperitoneal rectal cancer represents a significant clinical challenge, and currently, the standard treatment is based on neoadjuvant chemoradiation therapy (CRT) followed by radical surgical resection with total mesorectal excision (TME). In the last 30 years, its management has undergone significant changes due to the improvement of complementary radio- and chemotherapy treatments, the improvement of minimally invasive surgical approaches and the diffusion of organ-sparing approaches, such as nonoperative management, commonly called "watch and wait" (NOM) and local excision (LE), in highly selected patients who achieve a major or complete response to neoadjuvant CRT. This review aimed to critically examine the efficacy and oncological safety of NOM and LE compared to those of standard TME in rectal cancer patients after neoadjuvant CRT. Both the pros and cons of these approaches were strictly analyzed, providing a comprehensive and critical overview of these novel management strategies for rectal cancer.


Subject(s)
Neoadjuvant Therapy , Rectal Neoplasms , Rectal Neoplasms/therapy , Rectal Neoplasms/radiotherapy , Humans , Watchful Waiting , Chemoradiotherapy , Treatment Outcome , Chemoradiotherapy, Adjuvant
2.
Radiat Oncol ; 19(1): 87, 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38956690

ABSTRACT

BACKGROUND AND PURPOSE: Various deep learning auto-segmentation (DLAS) models have been proposed, some of which have been commercialized. However, the issue of performance degradation is notable when pretrained models are deployed in the clinic. This study aims to enhance precision of a popular commercial DLAS product in rectal cancer radiotherapy by localized fine-tuning, addressing challenges in practicality and generalizability in real-world clinical settings. MATERIALS AND METHODS: A total of 120 Stage II/III mid-low rectal cancer patients were retrospectively enrolled and divided into three datasets: training (n = 60), external validation (ExVal, n = 30), and generalizability evaluation (GenEva, n = 30) datasets respectively. The patients in the training and ExVal dataset were acquired on the same CT simulator, while those in GenEva were on a different CT simulator. The commercial DLAS software was first localized fine-tuned (LFT) for clinical target volume (CTV) and organs-at-risk (OAR) using the training data, and then validated on ExVal and GenEva respectively. Performance evaluation involved comparing the LFT model with the vendor-provided pretrained model (VPM) against ground truth contours, using metrics like Dice similarity coefficient (DSC), 95th Hausdorff distance (95HD), sensitivity and specificity. RESULTS: LFT significantly improved CTV delineation accuracy (p < 0.05) with LFT outperforming VPM in target volume, DSC, 95HD and specificity. Both models exhibited adequate accuracy for bladder and femoral heads, and LFT demonstrated significant enhancement in segmenting the more complex small intestine. We did not identify performance degradation when LFT and VPM models were applied in the GenEva dataset. CONCLUSIONS: The necessity and potential benefits of LFT DLAS towards institution-specific model adaption is underscored. The commercial DLAS software exhibits superior accuracy once localized fine-tuned, and is highly robust to imaging equipment changes.


Subject(s)
Deep Learning , Organs at Risk , Radiotherapy Planning, Computer-Assisted , Rectal Neoplasms , Humans , Rectal Neoplasms/radiotherapy , Rectal Neoplasms/pathology , Organs at Risk/radiation effects , Retrospective Studies , Radiotherapy Planning, Computer-Assisted/methods , Female , Male , Middle Aged , Aged , Radiotherapy Dosage , Tomography, X-Ray Computed , Adult , Radiotherapy, Intensity-Modulated/methods
3.
Cancer Radiother ; 28(3): 293-307, 2024 Jun.
Article in French | MEDLINE | ID: mdl-38876938

ABSTRACT

PURPOSE: The increased risk of second cancer after prostate radiotherapy is a debated clinical concern. The objective of the study was to assess the risk of occurrence of second cancers after prostate radiation therapy based on the analysis the literature, and to identify potential factors explaining the discrepancies in results between studies. MATERIALS AND METHODS: A review of the literature was carried out, comparing the occurrence of second cancers in patients all presenting with prostate cancer, treated or not by radiation. RESULTS: This review included 30 studies reporting the occurrence of second cancers in 2,112,000 patients treated or monitored for localized prostate cancer, including 1,111,000 by external radiation therapy and 103,000 by brachytherapy. Regarding external radiation therapy, the average follow-up was 7.3years. The majority of studies (80%) involving external radiation therapy, compared to no external radiation therapy, showed an increased risk of second cancers with a hazard ratio ranging from 1.13 to 4.9, depending on the duration of the follow-up. The median time to the occurrence of these second cancers after external radiotherapy ranged from 4 to 6years. An increased risk of second rectal and bladder cancer was observed in 52% and 85% of the studies, respectively. Considering a censoring period of more than 10 years after irradiation, 57% and 100% of the studies found an increased risk of rectal and bladder cancer, without any impact in overall survival. Studies of brachytherapy did not show an increased risk of second cancer. However, these comparative studies, most often old and retrospective, had many methodological biases. CONCLUSION: Despite numerous methodological biases, prostate external radiation therapy appears associated with a moderate increase in the risk of second pelvic cancer, in particular bladder cancer, without impacting survival. Brachytherapy does not increase the risk of a second cancer.


Subject(s)
Brachytherapy , Neoplasms, Radiation-Induced , Neoplasms, Second Primary , Prostatic Neoplasms , Humans , Male , Prostatic Neoplasms/radiotherapy , Neoplasms, Second Primary/etiology , Neoplasms, Second Primary/epidemiology , Neoplasms, Radiation-Induced/etiology , Neoplasms, Radiation-Induced/epidemiology , Brachytherapy/adverse effects , Brachytherapy/methods , Urinary Bladder Neoplasms/radiotherapy , Urinary Bladder Neoplasms/etiology , Rectal Neoplasms/radiotherapy , Rectal Neoplasms/etiology
5.
Dermatol Online J ; 30(1)2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38762867

ABSTRACT

Osteonecrosis of the jaw is a recognized complication associated with bevacizumab. Here, we present a patient with squamous cell carcinoma of the tonsil who experienced minimal skin fibrosis following intensity-modulated radiation therapy. Subsequently, the patient developed rectal adenocarcinoma and encountered osteonecrosis of the jaw after receiving two cycles of bevacizumab. Close monitoring, accompanied by thorough examination to detect early signs of osteonecrosis of the jaw, should be considered for patients who have undergone radiation therapy in the head and neck region and are receiving bevacizumab or other medications known to be associated with osteonecrosis of the jaw.


Subject(s)
Bevacizumab , Carcinoma, Squamous Cell , Radiotherapy, Intensity-Modulated , Tonsillar Neoplasms , Humans , Bevacizumab/adverse effects , Bevacizumab/therapeutic use , Carcinoma, Squamous Cell/radiotherapy , Carcinoma, Squamous Cell/drug therapy , Radiotherapy, Intensity-Modulated/adverse effects , Tonsillar Neoplasms/radiotherapy , Tonsillar Neoplasms/drug therapy , Male , Osteonecrosis/chemically induced , Adenocarcinoma/drug therapy , Adenocarcinoma/radiotherapy , Rectal Neoplasms/drug therapy , Rectal Neoplasms/radiotherapy , Antineoplastic Agents, Immunological/adverse effects , Middle Aged , Jaw Diseases/chemically induced
7.
Dis Colon Rectum ; 67(6): 782-795, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38701503

ABSTRACT

BACKGROUND: A variety of definitions for a clinical near-complete response after neoadjuvant (chemo) radiotherapy for rectal cancer are currently used. This variety leads to inconsistency in clinical practice, long-term outcome, and trial enrollment. OBJECTIVE: The aim of this study was to reach expert-based consensus on the definition of a clinical near-complete response after (chemo) radiotherapy. DESIGN: A modified Delphi process, including a systematic review, 3 surveys, and 2 meetings, was performed with an international expert panel consisting of 7 surgeons and 4 radiologists. The surveys consisted of individual features, statements, and feature combinations (endoscopy, T2-weighted MRI, and diffusion-weighted MRI). SETTING: The modified Delphi process was performed in an online setting; all 3 surveys were completed online by the expert panel, and both meetings were hosted online. MAIN OUTCOME MEASURES: The main outcome was to reach consensus (80% or more agreement). RESULTS: The expert panel reached consensus on a 3-tier categorization of the near-complete response category based on the likelihood of the response to evolve into a clinical complete response after a longer waiting interval. The panelists agreed that a near-complete response is a temporary entity only to be used in the first 6 months after (chemo)radiotherapy. Furthermore, consensus was reached that the lymph node status should be considered when deciding on a near-complete response and that biopsies are not always needed when a near-complete response is found. No consensus was reached on whether primary staging characteristics have to be taken into account when deciding on a near-complete response. LIMITATIONS: This 3-tier subcategorization is expert-based; therefore, there is no supporting evidence for this subcategorization. Also, it is unclear whether this subcategorization can be generalized into clinical practice. CONCLUSIONS: Consensus was reached on the use of a 3-tier categorization of a near-complete response, which can be helpful in daily practice as guidance for treatment and to inform patients with a near-complete response on the likelihood of successful organ preservation. See Video Abstract. UN CONSENSO INTERNACIONAL BASADO EN EXPERTOS ACERCA DE LA DEFINICIN DE UNA RESPUESTA CLNICA CASI COMPLETA DESPUS DE QUIMIORADIOTERAPIA NEOADYUVANTE CONTRA EL CNCER DE RECTO: ANTECEDENTES:Actualmente, se utilizan una variedad de definiciones para una respuesta clínica casi completa después de quimioradioterapia neoadyuvante contra el cáncer de recto. Esta variedad resulta en inconsistencia en la práctica clínica, los resultados a largo plazo y la inscripción en ensayos.OBJETIVO:El objetivo de este estudio fue llegar a un consenso de expertos sobre la definición de una respuesta clínica casi completa después de quimioradioterapia.DISEÑO:Se realizó un proceso Delphi modificado que incluyó una revisión sistemática, 3 encuestas y 2 reuniones con un panel internacional de expertos compuesto por siete cirujanos y 4 radiólogos. Las encuestas consistieron en características individuales, declaraciones y combinaciones de características (endoscopía, T2W-MRI y DWI).AJUSTE:El proceso Delphi modificado se realizó en un entorno en línea; el panel de expertos completó las tres encuestas en línea y ambas reuniones se realizaron en línea.PRINCIPALES MEDIDAS DE RESULTADO:El resultado principal fue llegar a un consenso (≥80% de acuerdo).RESULTADOS:El panel de expertos llegó a un consenso sobre una categorización de tres niveles de la categoría de respuesta casi completa basada en la probabilidad de que la respuesta evolucione hacia una respuesta clínica completa después de un intervalo de espera más largo. Los panelistas coincidieron en que una respuesta casi completa es una entidad temporal que sólo debe utilizarse en los primeros 6 meses después de la quimioradioterapia. Además, se llegó a un consenso en que se debe considerar el estado de los nódulos linfáticos al decidir sobre una respuesta casi completa y que no siempre se necesitan biopsias cuando se encuentra una respuesta casi completa. No se llegó a un consenso sobre si se deben tener en cuenta las características primarias de estadificación al decidir una respuesta casi completa.LIMITACIONES:Esta subcategorización de 3 niveles está basada en expertos; por lo tanto, no hay evidencia que respalde esta subcategorización. Además, no está claro si esta subcategorización puede generalizarse a la práctica clínica.CONCLUSIONES:Se alcanzó consenso sobre el uso de una categorización de 3 niveles de una respuesta casi completa que puede ser útil en la práctica diaria como guía para el tratamiento y para informar a los pacientes con una respuesta casi completa sobre la probabilidad de una preservación exitosa del órgano. (Traducción - Dr. Aurian Garcia Gonzalez).


Subject(s)
Consensus , Delphi Technique , Neoadjuvant Therapy , Rectal Neoplasms , Humans , Rectal Neoplasms/therapy , Rectal Neoplasms/pathology , Rectal Neoplasms/radiotherapy , Neoadjuvant Therapy/methods , Chemoradiotherapy/methods , Treatment Outcome , Diffusion Magnetic Resonance Imaging/methods
9.
Biomolecules ; 14(4)2024 Apr 06.
Article in English | MEDLINE | ID: mdl-38672465

ABSTRACT

The IFN-type-I pathway is involved in radiotherapy (RT)-mediated immune responses. Large RT fractions have been suggested to potently induce this pathway. Neoadjuvant hypofractionated short-course (scRT) and conventional long-course (lcRT) RT applied for the treatment of locally advanced rectal adenocarcinoma patients provides a unique model to address the immuno-stimulatory properties of RT on a systemic level. We prospectively analyzed the IFNß plasma levels and lymphocyte counts (LCs) of rectal adenocarcinoma patients before and after treatment with scRT (n = 22) and lcRT (n = 40). Flow cytometry was conducted to assess the effects on lymphocytic subpopulations in a subset of 20 patients. A statistically significant increase in the post-RT IFNß plasma levels was noted in patients undergoing scRT (p = 0.004). Improved pathological tumor regression was associated with elevated post-RT IFNß levels (p = 0.003). Although all patients experienced substantial lymphopenia after treatment, the post-RT LC of patients treated with scRT were significantly higher compared to lcRT (p = 0.001). Patients undergoing scRT displayed significantly lower percentages of regulatory CD4+/CD25+ T-cells after therapy (p = 0.02). scRT enables effective stimulation of the IFN-type-I pathway on a systemic level and confers decreased lymphocytic cytotoxicity and limited regulatory T-cell activation compared to lcRT, supporting its increasing role in immuno-RT trials.


Subject(s)
Adenocarcinoma , Neoadjuvant Therapy , Rectal Neoplasms , Humans , Rectal Neoplasms/radiotherapy , Rectal Neoplasms/immunology , Rectal Neoplasms/pathology , Rectal Neoplasms/blood , Male , Female , Middle Aged , Adenocarcinoma/radiotherapy , Adenocarcinoma/immunology , Adenocarcinoma/pathology , Aged , Radiation Dose Hypofractionation , Adult , Interferon-beta/therapeutic use , Interferon-beta/blood , Interferon Type I/blood , Lymphocyte Count
10.
Int Immunopharmacol ; 132: 111779, 2024 May 10.
Article in English | MEDLINE | ID: mdl-38581987

ABSTRACT

This study aimed to investigate the molecular mechanism of the effect of PDCD4 on radiotherapy-induced acute kidney injury (AKI) in rectal cancer through the regulation of FGR/NF-κB signaling. Differentially expressed genes were identified using Gene Expression Omnibus (GEO) datasets (GSE90627 for rectal cancer and GSE145085 for AKI) and R software. The human renal tubular epithelial cell line, HK-2, was used to establish an in vitro model of radiotherapy-induced AKI. RT-qPCR and western blotting were used to detect gene and protein expression levels, respectively. Cell proliferation and apoptosis were assessed using the CCK-8 assay and flow cytometry, respectively. The malondialdehyde and superoxide dismutase levels in the cell culture supernatants were determined. Additionally, an in vivo AKI model was established using BALB/c mice, and kidney tissue morphology, expression of the renal injury molecule KIM-1, apoptosis of renal tubular cells, and TAS and TOS in serum were evaluated. Bioinformatics analysis revealed the upregulated expression of PDCD4 in AKI. In vitro experiments demonstrated that PDCD4 induced apoptosis in renal tubular cells by promoting FGR expression, which activated the NF-κB signaling pathway and triggered an oxidative stress response. In vivo animal experiments confirmed that PDCD4 promoted oxidative stress response and radiotherapy-induced AKI through the activation of the FGR/NF-κB signaling pathway. Silencing PDCD4 attenuated radiotherapy-induced AKI. Our findings suggest that PDCD4 may induce radiotherapy-induced AKI in rectal cancer by promoting FGR expression, activating the NF-κB signaling pathway, and triggering an oxidative stress response.


Subject(s)
Acute Kidney Injury , Apoptosis Regulatory Proteins , Mice, Inbred BALB C , NF-kappa B , Oxidative Stress , RNA-Binding Proteins , Rectal Neoplasms , Signal Transduction , Animals , Humans , Acute Kidney Injury/metabolism , Acute Kidney Injury/genetics , NF-kappa B/metabolism , Apoptosis Regulatory Proteins/metabolism , Apoptosis Regulatory Proteins/genetics , RNA-Binding Proteins/genetics , RNA-Binding Proteins/metabolism , Mice , Rectal Neoplasms/radiotherapy , Rectal Neoplasms/genetics , Apoptosis , Male , Cell Line
11.
BMC Cancer ; 24(1): 501, 2024 Apr 19.
Article in English | MEDLINE | ID: mdl-38641773

ABSTRACT

BACKGROUND: For patients with locally advanced rectal cancer (LARC), total neoadjuvant therapy (TNT), namely, intensifying preoperative treatment through the integration of radiotherapy and systemic chemotherapy before surgery, was commonly recommended as the standard treatment. However, the risk of distant metastasis at 3 years remained higher than 20%, and the complete response (CR) rate was less than 30%. Several clinical trials had suggested a higher complete response rate when combining single-agent immunotherapy with short-course radiotherapy (SCRT). The CheckMate 142 study had shown encouraging outcomes of dual immunotherapy and seemingly comparable toxicity for CRC compared with single-agent immunotherapy in historical results. Therefore, dual immunotherapy might be more feasible in conjunction with the TNT paradigm of SCRT. We performed a phase II study to investigate whether the addition of a dual immune checkpoint inhibitor bispecific antibody, Cadonilimab, to SCRT combined with chemotherapy might further increase the clinical benefit and prognosis for LARC patients. METHODS: This single-arm, multicenter, prospective, phase II study included patients with pathologically confirmed cT3-T4N0 or cT2-4N + rectal adenocarcinoma with an ECOG performance score of 0 or 1. Bispecific antibody immunotherapy was added to SCRT combined with chemotherapy. Patients enrolled would be treated with SCRT (25 Gy in five fractions over 1 week) for the pelvic cavity, followed by 4 cycles of CAPOX or 6 cycles of mFOLFOX and Cadonilimab. The primary endpoint was the CR rate, which was the ratio of the pathological CR rate plus the clinical CR rate. The secondary endpoints included local-regional control, distant metastasis, disease-free survival, overall survival, toxicity profile, quality of life and functional outcome of the rectum. To detect an increase in the complete remission rate from 21.8% to 40% with 80% power, 50 patients were needed. DISCUSSION: This study would provide evidence on the efficacy and safety of SCRT plus bispecific antibody immunotherapy combined with chemotherapy as neoadjuvant therapy for patients with LARC, which might be used as a candidate potential therapy in the future. TRIAL REGISTRATION: This phase II trial was prospectively registered at ClinicalTrials.gov, under the identifier NCT05794750.


Subject(s)
Rectal Neoplasms , Rectum , Humans , Rectum/pathology , Prospective Studies , Quality of Life , Rectal Neoplasms/drug therapy , Rectal Neoplasms/radiotherapy , Neoadjuvant Therapy/methods , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Chemoradiotherapy/methods , Neoplasm Staging , Clinical Trials, Phase II as Topic , Multicenter Studies as Topic
13.
J Radiat Res ; 65(3): 379-386, 2024 May 23.
Article in English | MEDLINE | ID: mdl-38604182

ABSTRACT

The aim of the present study was to report the feasibility of proton beam reirradiation for patients with locally recurrent rectal cancer (LRRC) with prior pelvic irradiation. The study population included patients who were treated with proton beam therapy (PBT) for LRRC between 2008 and December 2019 in our institution. Those who had a history of distant metastases of LRRC, with or without treatment, before reirradiation, were excluded. Overall survival (OS), progression-free survival (PFS) and local control (LC) were estimated using the Kaplan-Meier method. Ten patients were included in the present study. The median follow-up period was 28.7 months, and the median total dose of prior radiotherapy (RT) was 50 Gy (range, 30 Gy-74.8 Gy). The median time from prior RT to reirradiation was 31.5 months (range, 8.1-96.6 months), and the median reirradiation dose was 72 Gy (relative biological effectiveness) (range, 56-77 Gy). The 1-year/2-year OS, PFS and LC rates were 100%/60.0%, 20.0%/10.0% and 70.0%/58.3%, respectively, with a median survival time of 26.0 months. Seven patients developed a Grade 1 acute radiation dermatitis, and no Grade ≥ 2 acute toxicity was recorded. Grade ≥ 3 late toxicity was recorded in only one patient, who had developed a colostomy due to radiation-related intestinal bleeding. Reirradiation using PBT for LRRC patients who had previously undergone pelvic irradiation was feasible. However, the indications for PBT reirradiation for LRRC patients need to be considered carefully due to the risk of severe late GI toxicity.


Subject(s)
Neoplasm Recurrence, Local , Pelvis , Proton Therapy , Re-Irradiation , Rectal Neoplasms , Humans , Rectal Neoplasms/radiotherapy , Female , Middle Aged , Male , Proton Therapy/adverse effects , Aged , Neoplasm Recurrence, Local/radiotherapy , Pelvis/radiation effects , Adult , Radiotherapy Dosage , Aged, 80 and over , Treatment Outcome
14.
Expert Rev Mol Med ; 26: e14, 2024 Apr 16.
Article in English | MEDLINE | ID: mdl-38623751

ABSTRACT

Neoadjuvant radiotherapy (RT) is commonly used as standard treatment for rectal cancer. However, response rates are variable and survival outcomes remain poor, highlighting the need to develop new therapeutic strategies. Research is focused on identifying novel methods for sensitising rectal tumours to RT to enhance responses and improve patient outcomes. This can be achieved through harnessing tumour promoting effects of radiation or preventing development of radio-resistance in cancer cells. Many of the approaches being investigated involve targeting the recently published new dimensions of cancer hallmarks. This review article will discuss key radiation and targeted therapy combination strategies being investigated in the rectal cancer setting, with a focus on exploitation of mechanisms which target the hallmarks of cancer.


Subject(s)
Rectal Neoplasms , Humans , Rectal Neoplasms/radiotherapy , Rectal Neoplasms/therapy , Rectal Neoplasms/pathology , Rectal Neoplasms/drug therapy , Molecular Targeted Therapy , Neoadjuvant Therapy/methods , Combined Modality Therapy , Treatment Outcome , Animals
15.
Langenbecks Arch Surg ; 409(1): 133, 2024 Apr 20.
Article in English | MEDLINE | ID: mdl-38642125

ABSTRACT

PURPOSE: To assess the safety and efficacy of synchronous treatments for rectal (RC) and prostate (PC) cancers. METHODS: Single-center retrospective study (2007-2021) of patients treated with neoadjuvant radiotherapy (RT) and total mesorectal excision (TME) for RC with synchronous PC treatment. The endpoints were 30-day postoperative severe complications, R0 resection rates, 3-year disease-free survival (DFS) and 3-year overall survival (OS). RESULTS: Among the 16 patients, 15 (93.7%) received neoadjuvant pelvic RT (40-50.4 Gray) followed by either transperineal high dose rate prostate brachytherapy (62.5%), prostate external RT boost (25.0%), or androgen deprivation therapy (ADT) alone (6.3%). One (6.3%) patient received neoadjuvant rectal brachytherapy and ADT. Pelvic RT was combined with chemotherapy in 87.5% of cases. TME was performed in all patients with low anterior resection (87.5%) or abdominoperineal resection (12.5%), primarily using minimally invasive surgery (87.5%). The R0 resection rate was 93.8%. Six (37.5%) patients experienced 30-day Clavien-Dindo grade IIIb complications, including one (7.1%) anastomotic leak. After a median follow-up of 39.0 months, 63.6% of diverting ileostomies were reversed. Three-year DFS from RC was 71.4% (CI 40.2-88.3) and 3-year OS was 84.4% (CI 95% 50.4-95.9). No PC recurrence or death occurred. CONCLUSIONS: Synchronous management of RC and PC with pelvic RT followed by curative prostate RT doses and TME showed acceptable morbidity and oncologic results. Prostate brachytherapy, the most commonly used treatment modality, allowed avoidance of prostatectomy and additional external RT to the rectum. PC should not limit the curative intent of RC, as all recurrences were from rectal origin.


Subject(s)
Prostatic Neoplasms , Rectal Neoplasms , Male , Humans , Prostatic Neoplasms/radiotherapy , Prostatic Neoplasms/surgery , Androgen Antagonists/therapeutic use , Retrospective Studies , Follow-Up Studies , Rectal Neoplasms/surgery , Rectal Neoplasms/radiotherapy , Neoadjuvant Therapy , Treatment Outcome
16.
Radiol Med ; 129(4): 615-622, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38512616

ABSTRACT

PURPOSE: The accurate prediction of treatment response in locally advanced rectal cancer (LARC) patients undergoing MRI-guided radiotherapy (MRIgRT) is essential for optimising treatment strategies. This multi-institutional study aimed to investigate the potential of radiomics in enhancing the predictive power of a known radiobiological parameter (Early Regression Index, ERITCP) to evaluate treatment response in LARC patients treated with MRIgRT. METHODS: Patients from three international sites were included and divided into training and validation sets. 0.35 T T2*/T1-weighted MR images were acquired during simulation and at each treatment fraction. The biologically effective dose (BED) conversion was used to account for different radiotherapy schemes: gross tumour volume was delineated on the MR images corresponding to specific BED levels and radiomic features were then extracted. Multiple logistic regression models were calculated, combining ERITCP with other radiomic features. The predictive performance of the different models was evaluated on both training and validation sets by calculating the receiver operating characteristic (ROC) curves. RESULTS: A total of 91 patients was enrolled: 58 were used as training, 33 as validation. Overall, pCR was observed in 25 cases. The model showing the highest performance was obtained combining ERITCP at BED = 26 Gy with a radiomic feature (10th percentile of grey level histogram, 10GLH) calculated at BED = 40 Gy. The area under ROC curve (AUC) of this combined model was 0.98 for training set and 0.92 for validation set, significantly higher (p = 0.04) than the AUC value obtained using ERITCP alone (0.94 in training and 0.89 in validation set). CONCLUSION: The integration of the radiomic analysis with ERITCP improves the pCR prediction in LARC patients, offering more precise predictive models to further personalise 0.35 T MRIgRT treatments of LARC patients.


Subject(s)
Radiomics , Rectal Neoplasms , Humans , Rectal Neoplasms/diagnostic imaging , Rectal Neoplasms/radiotherapy , Rectal Neoplasms/pathology , Magnetic Resonance Imaging/methods , Rectum , Neoadjuvant Therapy/methods , Retrospective Studies
17.
Neoplasia ; 51: 100984, 2024 05.
Article in English | MEDLINE | ID: mdl-38467087

ABSTRACT

INTRODUCTION: Colorectal cancer is the third most common cause of cancer death. Rectal cancer makes up a third of all colorectal cases. Treatment for locally advanced rectal cancer includes chemoradiation followed by surgery. We have previously identified ST6GAL1 as a cause of resistance to chemoradiation in vitro and hypothesized that it would be correlated with poor response in human derived models and human tissues. METHODS: Five organoid models were created from primary human rectal cancers and ST6GAL1 was knocked down via lentivirus transduction in one model. ST6GAL1 and Cleaved Caspase-3 (CC3) were assessed after chemoradiation via immunostaining. A tissue microarray (TMA) was created from twenty-six patients who underwent chemoradiation and had pre- and post-treatment specimens of rectal adenocarcinoma available at our institution. Immunohistochemistry was performed for ST6GAL1 and percent positive cancer cell staining was assessed and correlation with pathological grade of response was measured. RESULTS: Organoid models were treated with chemoradiation and both ST6GAL1 mRNA and protein significantly increased after treatment. The organoid model targeted with ST6GAL1 knockdown was found to have increased CC3 after treatment. In the tissue microarray, 42 percent of patient samples had an increase in percent tumor cell staining for ST6GAL1 after treatment. Post-treatment percent staining was associated with a worse grade of treatment response (p = 0.01) and increased staining post-treatment compared to pre-treatment was also associated with a worse response (p = 0.01). CONCLUSION: ST6GAL1 is associated with resistance to treatment in human rectal cancer and knockdown in an organoid model abrogated resistance to apoptosis caused by chemoradiation.


Subject(s)
Chemoradiotherapy , Rectal Neoplasms , beta-D-Galactoside alpha 2-6-Sialyltransferase , Humans , Antigens, CD , beta-D-Galactoside alpha 2-6-Sialyltransferase/drug effects , beta-D-Galactoside alpha 2-6-Sialyltransferase/metabolism , beta-D-Galactoside alpha 2-6-Sialyltransferase/radiation effects , Neoplasm Staging , Rectal Neoplasms/drug therapy , Rectal Neoplasms/genetics , Rectal Neoplasms/radiotherapy
18.
J Geriatr Oncol ; 15(3): 101739, 2024 04.
Article in English | MEDLINE | ID: mdl-38492350

ABSTRACT

INTRODUCTION: The choice of treatment for rectal cancer often differs in older and younger patients, with the rate of radiotherapy use lower among older adults. In our daily practice, when evaluating a frail older patient with rectal cancer, we usually choose to give less treatment. This may be due to concern that the patient will not be able to tolerate radiotherapy. The Geriatric 8 score (G8GS) is a guide to evaluating treatment tolerability as it relates to frailty in older adults with cancer. The aim of this study was to evaluate treatment outcomes and tolerability in older patients with rectal cancer treated with radiotherapy (RT) accompanied by G8GS. MATERIALS AND METHODS: Patients aged 65 and older with stage I-III rectal adenocarcinoma who were treated with RT and had a G8 evaluation were included in this multicenter retrospective study. Prognostic factors related to G8GS were calculated using Chi-square and logistic regression tests and survival rates were calculated by the Kaplan-Meier test using the SPSS v24.0 software. All p-values ≤0.05 were considered statistically significant. RESULTS: A total of 699 patients from 16 national institutions were evaluated. The median age was 72 years (range 65-96), and the median follow-up was 43 (range 1-190) months. Four hundred and fifty patients (64%) were categorized as frail with G8GS ≤14 points. Frail patients had higher ages (p = 0.001) and more comorbidities (p = 0.001). Ability to receive concomitant and/or adjuvant chemotherapy rates were significantly higher in fit patients (p = 0.002 and p = 0.001, respectively). No significant difference was observed in terms of grade 3-4 early and late toxicity for both groups. Cancer-related death was higher (p = 0.003), and 5- and 8-year survival rates were significantly lower (p = 0.001), in the frail group. Age and being frail were significantly associated with survival. DISCUSSION: Radiotherapy is a tolerable and effective treatment option for older adults with rectal cancer even with low G8GS. Being in the frail group according to G8GS and having multiple comorbidities was negatively associated with survival. Addressing the medical needs of frail patients through a comprehensive geriatric assessment prior to radiotherapy may improve G8GS, allowing for standard treatment and increased survival rates.


Subject(s)
Frailty , Rectal Neoplasms , Humans , Aged , Aged, 80 and over , Retrospective Studies , Treatment Outcome , Rectal Neoplasms/radiotherapy , Frailty/epidemiology , Comorbidity , Geriatric Assessment , Frail Elderly
20.
Cancer Biol Ther ; 25(1): 2317999, 2024 12 31.
Article in English | MEDLINE | ID: mdl-38445632

ABSTRACT

Rectal cancer accounts for the second highest cancer-related mortality, which is predominant in Western civilizations. The treatment for rectal cancers includes surgery, radiotherapy, chemotherapy, and immunotherapy. Radiotherapy, specifically external beam radiation therapy, is the most common way to treat rectal cancer because radiation not only limits cancer progression but also significantly reduces the risk of local recurrence. However, therapeutic radiation-induced radioresistance to rectal cancer cells and toxicity to normal tissues are major drawbacks. Therefore, understanding the mechanistic basis of developing radioresistance during and after radiation therapy would provide crucial insight to improve clinical outcomes of radiation therapy for rectal cancer patients. Studies by various groups have shown that radiotherapy-mediated changes in the tumor microenvironment play a crucial role in developing radioresistance. Therapeutic radiation-induced hypoxia and functional alterations in the stromal cells, specifically tumor-associated macrophage (TAM) and cancer-associated fibroblasts (CAF), play a crucial role in developing radioresistance. In addition, signaling pathways, such as - the PI3K/AKT pathway, Wnt/ß-catenin signaling, and the hippo pathway, modulate the radiation responsiveness of cancer cells. Different radiosensitizers, such as small molecules, microRNA, nanomaterials, and natural and chemical sensitizers, are being used to increase the effectiveness of radiotherapy. This review highlights the mechanism responsible for developing radioresistance of rectal cancer following radiotherapy and potential strategies to enhance the effectiveness of radiotherapy for better management of rectal cancer.


Subject(s)
Cancer-Associated Fibroblasts , MicroRNAs , Neoplasms, Second Primary , Rectal Neoplasms , Humans , Phosphatidylinositol 3-Kinases , Rectal Neoplasms/radiotherapy , Immunotherapy , Tumor Microenvironment
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