RARE DISEASE
Radiation proctitis
Radiation proctitis
Radiation proctitis
Drug discovery
2
drugs
With orphan designations
Overview
Radiation Proctitis
Radiation proctitis is rectal mucosal injury caused by pelvic radiation therapy, categorized into acute (during/within 3 months of treatment) and chronic (≥3 months post-treatment). Symptoms include diarrhea, rectal bleeding, urgency, and tenesmus. Chronic cases may lead to fibrosis, strictures, or fistulas. Management follows a stepwise approach, starting with anti-inflammatory agents and advancing to endoscopic or surgical interventions for refractory cases [1][5][8].
Therapies
Categories: rare disorders due to toxic effects, rare gastroenterological diseases
Research Papers
1,000 drug discovery papers about Radiation proctitis, with 1 first-in-class and 1 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
1,000 drug discovery papers about Radiation proctitis, with 1 first-in-class and 1 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2026-08-16 | Impact of Hydrogel Spacer on Radiation Proctitis After Prostate Cancer Radiation Therapy: A Large-Scale Claims Database Analysis.
We evaluated the real-world utility of hydrogel spacer placement for reducing radiation proctitis following prostate cancer radiation therapy using a large-scale claims database. We analyzed male patients from a Japanese administrative claims database (DeSC Database) who initiated primary radiation therapy between July 2018 and December 2024. Propensity score weighting using the average treatment effect on the treated method was applied to balance baseline characteristics between spacer users and nonusers. The primary endpoint was the occurrence of endoscopic gastrointestinal hemostasis, and the secondary endpoint was the diagnosis of radiation proctitis. Fine-Gray models were used to estimate subdistribution hazard ratios (sHRs) with death as a competing risk. Of 7860 eligible patients, 1754 (22.3%) underwent spacer placement. For the primary endpoint (endoscopic hemostasis), the spacer group showed a statistically significant lower risk (sHR 0.26; 95% CI, 0.10-0.69; P = .007). The cumulative incidence at 36 months was 0.8% in the spacer group versus 2.3% in the nonspacer group. For the secondary endpoint (diagnosed proctitis), the sHR was 0.29 (95% CI, 0.16-0.53; P < .001), with a 36-month cumulative incidence of 1.4% versus 4.8%, respectively. This large-scale real-world analysis demonstrates that hydrogel spacer placement is associated with a significantly lower incidence of severe radiation proctitis requiring endoscopic hemostasis.
2026-07-28 | Microbiota-nutrition sequential therapy for refractory radiation proctitis: A case report
BACKGROUNDGut dysbiosis is closely associated with radiation-induced intestinal injury.This study aimed to preliminarily assess the efficacy and safety of fecal microbiota transplantation (FMT) combined with immunomodulatory enteral nutrition (IEN) for the treatment of refractory radiation proctitis. CASE SUMMARYA 49-year-old woman with prior cervical cancer treated by hysterectomy 4 years earlier presented with left inguinal lymphadenopathy.Following radiotherapy, the patient experienced lower abdominal pain, diarrhea, and hematochezia, diagnosed as radiation enteritis.The patient underwent two FMT with adjunctive IEN support.Symptoms alleviated from Common Terminology Criteria for Adverse Events grade 3 proctitis to grade 2 after the first FMT, and further to grade 1 after the second.Nutritional and immune indices improved obviously: Body mass index (20.28kg/m²→24.34kg/m²), total protein (63.7 g/L→73.7 g/L), albumin (35.8 g/L→40 g/L), lymphocyte count (0.94× 10 9 /L→1.37 × 10 9 /L) and lymphocyte percentage (18.2%→34.8%)rose, while procalcitonin dropped from 0.07 ng/mL to 0.03 ng/mL.The Vienna Rectoscopy Score declined from 25 to 16 post-FMT1 and 5 post-FMT2.Pro-inflammatory cytokines tumor necrosis factor-α (2.29 pg/mL→1.51pg/mL), interferon (IFN)-γ (0.73 pg/mL→0.16pg/mL) and interleukin (IL)-6 (9.40 pg/mL→3.60 pg/mL) decreased significantly, while anti-inflammatory IL-4 (0.97 pg/mL→1.16pg/mL) and IL-10 (0.70 pg/mL→0.86 pg/mL) slightly increased.IL-2 and IL-1β rose mildly, and IL-8 elevated moderately.Sequential FMT restored gut Shannon diversity; principal coordinates analysis verified microbiota remodeling close to donor profiles, with reduced Escherichia-Shigella and enriched beneficial genera Faecalibacterium, Bacteroides and Ruminococcus. CONCLUSION 4 / 31In this patient, FMT combined with immunomodulatory nutrition was associated with restoration of gut microbiota, alleviation of symptoms, and improvement in nutritional and immune parameters in refractory radiation proctitis, suggesting a potential therapeutic strategy that warrants further validation.
2026-06-17 | Incidence and predictors of radiation proctitis or radiation cystitis after radiotherapy in patients with prostate cancer.
This study evaluated the cumulative incidences of radiation cystitis (RC) and radiation proctitis (RP) after radiotherapy (RT) for localised and metastatic prostate cancer (PCa). It also analysed potential risk factors associated with resultant emergency admissions. Between January 2001 and January 2023, 762 patients who underwent primary RT for localised PCa and low-volume metastatic hormone-sensitive PCa, as well as salvage or adjuvant RT after prostatectomy, were retrospectively analysed. The severities of RC and RP were assessed using the Common Terminology Criteria for Adverse Events version 5.0. Severe events were defined as grade 3 or higher. The median follow-up time was 59 months. The 5-year/10-year cumulative incidences of RC and severe RC were 11%/20% and 6.3%/12%, respectively. Among 58 patients with severe RC, 11 (19.0%) required endoscopic haemostasis. The 5-year/10-year cumulative incidences of RP and severe RP were 20%/21% and 7.5%/8.4%, respectively. Among 57 patients with severe RP, 38 (67%) required endoscopic haemostasis. Multivariable Cox regression analysis identified adjuvant or salvage RT as a predictor of RC; primary RT was identified as a predictor of RP. A bladder volume receiving >60 Gy of >25% was identified as a predictor of RC and severe RC. A rectal volume receiving >70 Gy of >10% was identified as a predictor of RP and severe RP. Antiplatelet medication was a significant risk factor for RC, RP, and severe events. Radiation cystitis and RP are common complications of RT in patients with PCa. Comprehensive counselling regarding these potential long-term adverse effects is imperative.
2026-06-10 | Single cells and spatial RNA profiling reveal that inflammatory fibroblasts arise from Edil3 stromal cells in the colon after irradiation.
Patients with cancer who are treated for tumors located in the abdominopelvic region may develop radiation proctitis. This condition is characterized by severe mucosal inflammation that can significantly impair quality of life. In the colon, it's now established that the stroma orchestrates epithelial, endothelial, and immune cell homeostasis and plays a pivotal role following an injury. A more comprehensive understanding of the underlying mechanisms responsible for digestive mucosa injury and regeneration processes would enable therapeutic targets to be identified for limiting or even treating digestive lesions caused by radiotherapy. In this work, single-cell RNA sequencing was combined with spatial transcriptomics (ST) for an in-depth characterization of colonic stromal cells, highlighting their heterogeneity, their specific functions and interactions in homeostasis, and changes they undergo following localized colon irradiation. The present study identifies the Edil3 marker, (EGF-like repeats and discoidin domains 3), that distinguishes the most abundant stromal population, alongside the previously characterized trophocytes and telocytes. We propose the term "mesitocytes", from the ancient Greek "mesítês" ("intermediary"), for this stromal subtype, in accordance with both their position along the crypt axis and their role in the BMP/Wnt gradient. After irradiation, we demonstrate the deregulation of the stromal compartment, with an increase of genes involved in immune response, angiogenesis, and regenerative epithelial process. Specifically in the ulcerated area, Edil3 mesitocytes and telocytes are no longer detected by ST. Instead, inflammation-associated fibroblasts (IAFs) emerge, characterized by a distinct transcriptomic signature, including Ereg, Igfbp5, Il11 and C3. This feature is substantiated by analysis of human transcriptomic data which underscores the significance of our findings. Cell fate analysis further clarifies the origins of IAFs, identifying Edil3 mesitocytes as their main source. Furthermore, we observe that IAFs cooperate with endothelial cells, and we also demonstrate IAF-specific molecules involvement in epithelial disruption and endothelial activation, suggesting their key role in disease progression.
2026-05-03 | Temporal Patterns and Resolution of Toxicities Following Hypofractionated Salvage Radiotherapy for Biochemical Recurrence of Prostate Cancer After Prostatectomy.
Hypofractionated salvage radiotherapy is increasingly used for biochemical recurrence of prostate cancer post-prostatectomy, yet its toxicity profile remains underexplored. This study evaluates the incidence, timing, and resolution of treatment-related toxicities in this setting. A retrospective cohort study of 403 men receiving hypofractionated salvage radiotherapy (62.5 Gy in 25 fractions) from 2017 to 2024 was conducted. Toxicities, categorized as genitourinary (hematuria, urinary incontinence, frequency, dysuria) or gastrointestinal (rectal bleeding, diarrhea, proctitis, nausea), were graded (1-3) using CTCAE-based criteria. Outcomes included any-time incidence, Kaplan-Meier time-to-first-event estimates (12- and 24-month cumulative incidence), and first-onset timing. Episode-level analyses merged events ≤ 30 days apart, assessing resolution and intervention. Median follow-up was 18.2 months. Any-grade genitourinary and gastrointestinal toxicities occurred in 34.2% and 24.6% of patients, respectively (24-month incidence: genitourinary 40.4%; gastrointestinal 28.9%). Grade 2+ toxicities were less frequent (genitourinary 9.7%; gastrointestinal 7.7%), with Grade 3+ rare (genitourinary 1.7%; gastrointestinal 0.7%). In terms of patient-level ever-event incidences, common symptoms included urinary incontinence (20.3%), rectal bleeding (19.9%), and hematuria (13.9%). Urinary toxicities predominantly onset at 6-12 months, whereas rectal bleeding and hematuria emerged later (≥ 12 months). Approximately two-thirds of Grade 2+ episodes resolved (e.g., urinary incontinence, 66.7%; rectal bleeding, 69.2%), with median resolution times of 3.0-8.4 months. With a median follow-up of 18.2 months, hypofractionated salvage radiotherapy demonstrates favorable short-to-intermediate term tolerability, with infrequent severe toxicities. Vigilant monitoring for late-onset rectal bleeding and hematuria is recommended during the 6-24 months after treatment to optimize patient management. Longer follow-up is required to confirm long-term safety.
2026-08-16 | Impact of Hydrogel Spacer on Radiation Proctitis After Prostate Cancer Radiation Therapy: A Large-Scale Claims Database Analysis.
We evaluated the real-world utility of hydrogel spacer placement for reducing radiation proctitis following prostate cancer radiation therapy using a large-scale claims database. We analyzed male patients from a Japanese administrative claims database (DeSC Database) who initiated primary radiation therapy between July 2018 and December 2024. Propensity score weighting using the average treatment effect on the treated method was applied to balance baseline characteristics between spacer users and nonusers. The primary endpoint was the occurrence of endoscopic gastrointestinal hemostasis, and the secondary endpoint was the diagnosis of radiation proctitis. Fine-Gray models were used to estimate subdistribution hazard ratios (sHRs) with death as a competing risk. Of 7860 eligible patients, 1754 (22.3%) underwent spacer placement. For the primary endpoint (endoscopic hemostasis), the spacer group showed a statistically significant lower risk (sHR 0.26; 95% CI, 0.10-0.69; P = .007). The cumulative incidence at 36 months was 0.8% in the spacer group versus 2.3% in the nonspacer group. For the secondary endpoint (diagnosed proctitis), the sHR was 0.29 (95% CI, 0.16-0.53; P < .001), with a 36-month cumulative incidence of 1.4% versus 4.8%, respectively. This large-scale real-world analysis demonstrates that hydrogel spacer placement is associated with a significantly lower incidence of severe radiation proctitis requiring endoscopic hemostasis.
2026-07-28 | Microbiota-nutrition sequential therapy for refractory radiation proctitis: A case report
BACKGROUNDGut dysbiosis is closely associated with radiation-induced intestinal injury.This study aimed to preliminarily assess the efficacy and safety of fecal microbiota transplantation (FMT) combined with immunomodulatory enteral nutrition (IEN) for the treatment of refractory radiation proctitis. CASE SUMMARYA 49-year-old woman with prior cervical cancer treated by hysterectomy 4 years earlier presented with left inguinal lymphadenopathy.Following radiotherapy, the patient experienced lower abdominal pain, diarrhea, and hematochezia, diagnosed as radiation enteritis.The patient underwent two FMT with adjunctive IEN support.Symptoms alleviated from Common Terminology Criteria for Adverse Events grade 3 proctitis to grade 2 after the first FMT, and further to grade 1 after the second.Nutritional and immune indices improved obviously: Body mass index (20.28kg/m²→24.34kg/m²), total protein (63.7 g/L→73.7 g/L), albumin (35.8 g/L→40 g/L), lymphocyte count (0.94× 10 9 /L→1.37 × 10 9 /L) and lymphocyte percentage (18.2%→34.8%)rose, while procalcitonin dropped from 0.07 ng/mL to 0.03 ng/mL.The Vienna Rectoscopy Score declined from 25 to 16 post-FMT1 and 5 post-FMT2.Pro-inflammatory cytokines tumor necrosis factor-α (2.29 pg/mL→1.51pg/mL), interferon (IFN)-γ (0.73 pg/mL→0.16pg/mL) and interleukin (IL)-6 (9.40 pg/mL→3.60 pg/mL) decreased significantly, while anti-inflammatory IL-4 (0.97 pg/mL→1.16pg/mL) and IL-10 (0.70 pg/mL→0.86 pg/mL) slightly increased.IL-2 and IL-1β rose mildly, and IL-8 elevated moderately.Sequential FMT restored gut Shannon diversity; principal coordinates analysis verified microbiota remodeling close to donor profiles, with reduced Escherichia-Shigella and enriched beneficial genera Faecalibacterium, Bacteroides and Ruminococcus. CONCLUSION 4 / 31In this patient, FMT combined with immunomodulatory nutrition was associated with restoration of gut microbiota, alleviation of symptoms, and improvement in nutritional and immune parameters in refractory radiation proctitis, suggesting a potential therapeutic strategy that warrants further validation.
2026-06-17 | Incidence and predictors of radiation proctitis or radiation cystitis after radiotherapy in patients with prostate cancer.
This study evaluated the cumulative incidences of radiation cystitis (RC) and radiation proctitis (RP) after radiotherapy (RT) for localised and metastatic prostate cancer (PCa). It also analysed potential risk factors associated with resultant emergency admissions. Between January 2001 and January 2023, 762 patients who underwent primary RT for localised PCa and low-volume metastatic hormone-sensitive PCa, as well as salvage or adjuvant RT after prostatectomy, were retrospectively analysed. The severities of RC and RP were assessed using the Common Terminology Criteria for Adverse Events version 5.0. Severe events were defined as grade 3 or higher. The median follow-up time was 59 months. The 5-year/10-year cumulative incidences of RC and severe RC were 11%/20% and 6.3%/12%, respectively. Among 58 patients with severe RC, 11 (19.0%) required endoscopic haemostasis. The 5-year/10-year cumulative incidences of RP and severe RP were 20%/21% and 7.5%/8.4%, respectively. Among 57 patients with severe RP, 38 (67%) required endoscopic haemostasis. Multivariable Cox regression analysis identified adjuvant or salvage RT as a predictor of RC; primary RT was identified as a predictor of RP. A bladder volume receiving >60 Gy of >25% was identified as a predictor of RC and severe RC. A rectal volume receiving >70 Gy of >10% was identified as a predictor of RP and severe RP. Antiplatelet medication was a significant risk factor for RC, RP, and severe events. Radiation cystitis and RP are common complications of RT in patients with PCa. Comprehensive counselling regarding these potential long-term adverse effects is imperative.
2026-06-10 | Single cells and spatial RNA profiling reveal that inflammatory fibroblasts arise from Edil3 stromal cells in the colon after irradiation.
Patients with cancer who are treated for tumors located in the abdominopelvic region may develop radiation proctitis. This condition is characterized by severe mucosal inflammation that can significantly impair quality of life. In the colon, it's now established that the stroma orchestrates epithelial, endothelial, and immune cell homeostasis and plays a pivotal role following an injury. A more comprehensive understanding of the underlying mechanisms responsible for digestive mucosa injury and regeneration processes would enable therapeutic targets to be identified for limiting or even treating digestive lesions caused by radiotherapy. In this work, single-cell RNA sequencing was combined with spatial transcriptomics (ST) for an in-depth characterization of colonic stromal cells, highlighting their heterogeneity, their specific functions and interactions in homeostasis, and changes they undergo following localized colon irradiation. The present study identifies the Edil3 marker, (EGF-like repeats and discoidin domains 3), that distinguishes the most abundant stromal population, alongside the previously characterized trophocytes and telocytes. We propose the term "mesitocytes", from the ancient Greek "mesítês" ("intermediary"), for this stromal subtype, in accordance with both their position along the crypt axis and their role in the BMP/Wnt gradient. After irradiation, we demonstrate the deregulation of the stromal compartment, with an increase of genes involved in immune response, angiogenesis, and regenerative epithelial process. Specifically in the ulcerated area, Edil3 mesitocytes and telocytes are no longer detected by ST. Instead, inflammation-associated fibroblasts (IAFs) emerge, characterized by a distinct transcriptomic signature, including Ereg, Igfbp5, Il11 and C3. This feature is substantiated by analysis of human transcriptomic data which underscores the significance of our findings. Cell fate analysis further clarifies the origins of IAFs, identifying Edil3 mesitocytes as their main source. Furthermore, we observe that IAFs cooperate with endothelial cells, and we also demonstrate IAF-specific molecules involvement in epithelial disruption and endothelial activation, suggesting their key role in disease progression.
2026-05-03 | Temporal Patterns and Resolution of Toxicities Following Hypofractionated Salvage Radiotherapy for Biochemical Recurrence of Prostate Cancer After Prostatectomy.
Hypofractionated salvage radiotherapy is increasingly used for biochemical recurrence of prostate cancer post-prostatectomy, yet its toxicity profile remains underexplored. This study evaluates the incidence, timing, and resolution of treatment-related toxicities in this setting. A retrospective cohort study of 403 men receiving hypofractionated salvage radiotherapy (62.5 Gy in 25 fractions) from 2017 to 2024 was conducted. Toxicities, categorized as genitourinary (hematuria, urinary incontinence, frequency, dysuria) or gastrointestinal (rectal bleeding, diarrhea, proctitis, nausea), were graded (1-3) using CTCAE-based criteria. Outcomes included any-time incidence, Kaplan-Meier time-to-first-event estimates (12- and 24-month cumulative incidence), and first-onset timing. Episode-level analyses merged events ≤ 30 days apart, assessing resolution and intervention. Median follow-up was 18.2 months. Any-grade genitourinary and gastrointestinal toxicities occurred in 34.2% and 24.6% of patients, respectively (24-month incidence: genitourinary 40.4%; gastrointestinal 28.9%). Grade 2+ toxicities were less frequent (genitourinary 9.7%; gastrointestinal 7.7%), with Grade 3+ rare (genitourinary 1.7%; gastrointestinal 0.7%). In terms of patient-level ever-event incidences, common symptoms included urinary incontinence (20.3%), rectal bleeding (19.9%), and hematuria (13.9%). Urinary toxicities predominantly onset at 6-12 months, whereas rectal bleeding and hematuria emerged later (≥ 12 months). Approximately two-thirds of Grade 2+ episodes resolved (e.g., urinary incontinence, 66.7%; rectal bleeding, 69.2%), with median resolution times of 3.0-8.4 months. With a median follow-up of 18.2 months, hypofractionated salvage radiotherapy demonstrates favorable short-to-intermediate term tolerability, with infrequent severe toxicities. Vigilant monitoring for late-onset rectal bleeding and hematuria is recommended during the 6-24 months after treatment to optimize patient management. Longer follow-up is required to confirm long-term safety.
Access all drug discovery papers and probability of success in trials forecasts:
Access all drug discovery papers and probability of success in trials forecasts:
Drug Discovery Landscape
2 orphan drug designations for Radiation proctitis.
2 orphan drug designations for Radiation proctitis.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
Sodium butyrate (rectal use) | small molecules | EMA | 2005-05-27 | — | Promefarm srl |
Short chain fatty acid enema | small molecules | FDA | 1997-08-19 | — | Richard I. Breuer, M.D. |
Let's accelerate rare disease drug discovery
Let's accelerate drug discovery
Get access to Explority AI's forecasts to outperform average preclinical success rates. Whether you're expanding your R&D pipeline, evaluating a partnership, or simply have a question — we'd love to hear from you.