Risk factors and dose-effects for bladder fistula, bleeding and cystitis after radiotherapy with imaged-guided adaptive brachytherapy for cervical cancer: An EMBRACE analysis

Spampinato, S.; Fokdal, Lars; Pötter, Richard; Haie-Méder, Christine; Lindegaard, Jacob Christian; Schmid, Maximilian; Sturdza, Alina; Jürgenliemk-Schulz, Ina M.; Mahantshetty, Umesh; Šegedin, Barbara; Bruheim, Kjersti; Hoskin, Peter; Rai, Bhavana; Huang, Fleur; Cooper, R.; Steen-Banasik, Elzbieta van der; Limbergen, Erik; Sundset, Marit; Westerveld, Henrike; Nout, Remi A.; Jensen, Nina Boje Kibsgaard; Kirisits, Christian; Kirchheiner, Kathrin; Tanderup, Kari

doi:10.1016/j.radonc.2021.01.019

Cited by 41 publications

(19 citation statements)

References 45 publications

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“…6,7 Although these therapeutic methods play an important role in treating cervical cancer, their side effects and drug resistance are still a challenge that needs to be overcome within clinical practice. 8,9 Among the traditional treatment methods, chemotherapy is useful in treating cervical cancer. Doxorubicin (DOX) is a clinically used chemotherapeutic drug, which has an inhibitory effect on a variety of tumors.…”

Section: Introductionmentioning

confidence: 99%

Indocyanine Green-Based Theranostic Nanoplatform for NIR Fluorescence Image-Guided Chemo/Photothermal Therapy of Cervical Cancer

Ma¹,

Alifu²,

Du³

et al. 2021

IJN

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Indocyanine green (ICG) is a favorable fluorescence nanoprobe for its strong NIR-I fluorescence emission and good photothermal capabilities. However, the stability and tumor targeting ability of ICG is poor, which limits its further applications. To further improve the photothermal and therapeutic efficiency of ICG, bovine serum albumin (BSA) was utilized to encapsulate the ICG and the chemotherapeutic drug doxorubicin (DOX) was loaded to form the BSA@ICG-DOX theranostic nanoplatform. Methods: In this study, ICG-loaded BSA nanoparticles (NPs) and the BSA@ICG-DOX NPs were fabricated using reprecipitation methods. Next, the tumour inhibition ability and biocompatibility of the NPs were evaluated. A subcutaneous xenografted nude mice model was established and imaging guided synergetic therapy was performed with the assistance of BSA@ICG-DOX NPs under 808 nm laser irradiation. Results: The BSA@ICG NPs exhibited strong NIR-I fluorescence emission, excellent photothermal properties, biocompatibility, and tumor targeting ability. To further improve the therapeutic efficiency, the chemotherapeutic drug doxorubicin (DOX) was loaded into the BSA@ICG NPs to form the BSA@ICG-DOX theranostic nanoplatform. The BSA@ICG-DOX NPs were spherical with an average size of ~194.7 nm. The NPs had high encapsulation efficiency (DOX: 19.96% and ICG: 60.57%), and drug loading content (DOX: 0.95% and ICG: 3.03%). Next, excellent NIR-I fluorescence and low toxicity of the BSA@ICG-DOX NPs were verified. Targeted NIR-I fluorescence images were obtained after intravenous injection of the NPs into the subcutaneous cervical tumors of the mice. Conclusion:To improve the anti-tumor efficiency of the ICG@BSA NPs, the chemotherapeutic drug DOX was loaded into the BSA@ICG NPs. The NIR excitation/emission and targeted BSA@ICG-DOX NPs enables high-performance diagnosis and chemo/photothermal therapy of subcutaneous cervical tumors, providing a promising approach for further biomedical applications.

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Section: Introductionmentioning

confidence: 99%

Indocyanine Green-Based Theranostic Nanoplatform for NIR Fluorescence Image-Guided Chemo/Photothermal Therapy of Cervical Cancer

Ma¹,

Alifu²,

Du³

et al. 2021

IJN

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“…Moreover, of note, tumor extension at diagnosis has been correlated with increased incidence of complications, such as fistulae (recto-vaginal and vesico-vaginal fistulae), which represent a therapeutic challenge in very locally advanced cervical cancers [ 13 , 14 , 15 ]. Therefore, the use of CCRT in bulky and very advanced cervical cancer, as in our case, has major risk.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, the use of CCRT in bulky and very advanced cervical cancer, as in our case, has major risk. In particular, it is often reported that bladder involvement and infiltration is associated with a strong fragility of vesical wall after radiation that almost constantly favors complications related to radiotherapy with consequent fistulae formation [ 14 , 16 , 17 ]. In addition, surgery after CCRT in such an advanced stage of disease may be related to more frequent late complications [ 18 ].…”

Section: Discussionmentioning

confidence: 99%

Diagnostic Framework of Pelvic Massive Necrosis with Peritonitis following Chemoradiation for Locally Advanced Cervical Cancer: When Is the Surgery Not Demandable? A Case Report and Literature Review

et al. 2022

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Concurrent platinum-based chemoradiation (CCRT) is the established treatment for locally advanced cervical cancer and has an acceptable toxicity. Radiation-induced necrosis of the uterus and pelvic tissue is a rare and usually late potential complication. Limited data are available about its management. Here, we describe a case of a patient affected by a locally advanced cervical cancer (stage IVA) who received CCRT, obtaining a partial response with persistence of bladder and rectal infiltration. Unfortunately, after the first brachytherapy dose, the patient developed a worsening clinical picture with fever and altered laboratory data indicative of sepsis; the computed tomography revealed a massive necrosis of the uterus with pelvic abscess and peritonitis. We performed a laparoscopic emergency surgery with removal of the necrotic tissue, supracervical hysterectomy, bilateral-oophorectomy, and abscess drainage. Thereafter, once the severe inflammatory condition was resolved, the patient underwent pelvic exenteration with palliative/curative intent. The postoperative PET/CT was negative for residual disease. However, the patient needed further hospitalization for re-occurrence of peritonitis with multiple abscesses. A careful diagnosis is crucial in locally advanced cervical cancer patients who, after CCRT, present persistent pain and problematic findings at imaging and laboratory parameters. In these cases, radiation-induced necrosis of the pelvis should be suspected. This case helps to clarify the central role of surgery, especially when actinic necrosis leads to complications such as abscess, fistulae, and extensive tissue destruction that cannot be conservatively medically handled. Laparoscopy represents an ideal approach to realizing the correct diagnosis, as well as enabling the performance of important therapeutic surgical procedures.

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“…Most recently, EMBRACE I published its results on risk factors and dose effects for bladder fistula and cystitis. They found that the crude incidence rate for bladder fistula greater than grade 1 was 0.7% and that an increase from 75 Gy to 80 Gy in bladder D2cm 3 resulted in an increase from 8% to 13% of cystitis greater than grade 1 [ 45 ].…”

Section: Discussionmentioning

confidence: 99%

MRI-Directed Brachytherapy for Cancer of the Uterine Cervix: A Case Report, Review, and Perspective on the Importance of Widespread Use of This Technological Advance in the United States

Ahmed¹,

Vijayakumar²,

Duggar³

et al. 2021

Cureus

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Cervical cancer remains a major health challenge in the United States (US), especially among the low socioeconomic and African American populations. The demographics of Mississippi constitute a relatively high percentage of this high-risk population. External beam radiation therapy (EBRT) combined with concurrent chemotherapy and followed by brachytherapy is the gold standard of treatment for stage IB3 through IVA cervical cancer. Arguably, brachytherapy is the most important component of this treatment process. Patterns of Care studies (PCS) and other more recent studies have shown that brachytherapy cannot be omitted or replaced by conventional or image-guided EBRT. The last decade has witnessed the expanding use of image-guided brachytherapy (IGBT). Studies have established the superiority of IGBT over point-based brachytherapy. MRI is associated with superior soft tissue definition compared with CT and is emerging as the new standard of care. The Gynaecological Groupe Européen de Curiethérapie and the European Society for Radiotherapy and Oncology [(GYN) GEC-ESTRO] have recommended that the dose be prescribed to the high-risk clinical target volume (HR-CTV). This volume includes residual tumor present at the time of brachytherapy, the cervix, and any gray areas seen on the scan. The (GYN) GEC-ESTRO has shown that a dose of >8500 cGy delivered in <50 days results in an approximate 10% increase in pelvic control (PC), disease-specific survival, and overall survival (OS) compared to historical controls. The normal tissue toxicity is comparable or better than historical controls as well. This dose, while maintaining normal tissue constraints, may only be achievable with a hybrid intracavitary/interstitial (IC/IS) needle device guided by MRI-based targeting. The University of Mississippi Medical Center (UMMC) has initiated an MRI-based cervical brachytherapy program and has treated 18 patients to date; our experience confirms the above findings. In this report, we propose that MRI guidance is necessary and a hybrid IC/IS needle device is required to achieve adequate dose coverages.

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Risk factors and dose-effects for bladder fistula, bleeding and cystitis after radiotherapy with imaged-guided adaptive brachytherapy for cervical cancer: An EMBRACE analysis

Cited by 41 publications

References 45 publications

Indocyanine Green-Based Theranostic Nanoplatform for NIR Fluorescence Image-Guided Chemo/Photothermal Therapy of Cervical Cancer

Indocyanine Green-Based Theranostic Nanoplatform for NIR Fluorescence Image-Guided Chemo/Photothermal Therapy of Cervical Cancer

Diagnostic Framework of Pelvic Massive Necrosis with Peritonitis following Chemoradiation for Locally Advanced Cervical Cancer: When Is the Surgery Not Demandable? A Case Report and Literature Review

MRI-Directed Brachytherapy for Cancer of the Uterine Cervix: A Case Report, Review, and Perspective on the Importance of Widespread Use of This Technological Advance in the United States

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