scholarly journals PROTECT: Prospective Phase-II-Trial Evaluating Adaptive Proton Therapy for Cervical Cancer to Reduce the Impact on Morbidity and the Immune System

Cancers ◽  
2021 ◽  
Vol 13 (20) ◽  
pp. 5179
Author(s):  
Anouk Corbeau ◽  
Remi A. Nout ◽  
Jan Willem M. Mens ◽  
Nanda Horeweg ◽  
Jérémy Godart ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Radiation Therapy ◽  
Phase Ii ◽  
Proton Therapy ◽  
Phase Ii Trial ◽  
Locally Advanced ◽  
External Beam Radiation ◽  
Beam Radiation ◽  
Intensity Modulated ◽  
The Impact

External beam radiation therapy (EBRT) with concurrent chemotherapy followed by brachytherapy is a very effective treatment for locally advanced cervical cancer (LACC). However, treatment-related toxicity is common and reduces the patient’s quality of life (QoL) and ability to complete treatment or undergo adjuvant therapies. Intensity modulated proton therapy (IMPT) enables a significant dose reduction in organs at risk (OAR), when compared to that of standard intensity-modulated radiation therapy (IMRT) or volumetric-modulated arc therapy (VMAT). However, clinical studies evaluating whether IMPT consequently reduces side effects for LACC are lacking. The PROTECT trial is a nonrandomized prospective multicenter phase-II-trial comparing clinical outcomes after IMPT or IMRT/VMAT in LACC. Thirty women aged >18 years with a histological diagnosis of LACC will be included in either the IMPT or IMRT/VMAT group. Treatment includes EBRT (45 Gy in 25 fractions of 1.8 Gy), concurrent five weekly cisplatin (40 mg/m2), and 3D image (MRI)-guided adaptive brachytherapy. The primary endpoint is pelvic bones Dmean and mean bowel V15Gy. Secondary endpoints include dosimetric parameters, oncological outcomes, health-related QoL, immune response, safety, and tolerability. This study provides the first data on the potential of IMPT to reduce OAR dose in clinical practice and improve toxicity and QoL for patients with LACC.

Radiation therapy for elderly patients with uterine cervical cancer: feasibility of curative treatment

2019 ◽  
Vol 29 (3) ◽  
pp. 622-629 ◽  
Author(s):  
Masaharu Hata
Keyword(s):  
Cervical Cancer ◽  
Radiation Therapy ◽  
Elderly Patients ◽  
Adult Population ◽  
Locally Advanced ◽  
Uterine Cervical Cancer ◽  
External Beam Radiation ◽  
Curative Treatment ◽  
Carbon Ions ◽  
Beam Radiation

As the average lifespan lengthens worldwide, and the older adult population increases, the number of elderly patients with uterine cervical cancer is increasing. Because intensive and invasive treatments, including surgery, are frequently unacceptable in elderly patients, cancer treatments for these patients must be carefully considered. Elderly patients have undergone radiation therapy as less-invasive curative treatment, and it has been shown to be safe and effective for local control of cervical cancer in this population, even among patients aged ≥80 years treated with curative radiation doses. Although concurrent chemoradiotherapy is the standard treatment for locally advanced cervical cancer, it is unclear whether the addition of chemotherapy to radiation therapy prolongs survival in elderly patients. Elderly patients treated with curative radiation therapy for cervical cancer might develop more therapy-related gastrointestinal and hematological toxicities and insufficiency fractures compared with younger patients. However, advanced techniques of radiation therapy (eg, intensity-modulated radiation therapy and volumetric modulated arc therapy with photons, charged-particle radiation therapy with protons and carbon ions in external-beam radiation therapy, and image-guided adaptive brachytherapy) can minimize radiation-induced toxicities and thus make curative treatment safer and more effective for elderly patients with uterine cervical cancer.

scholarly journals S0356: A Phase II Clinical and Prospective Molecular Trial With Oxaliplatin, Fluorouracil, and External-Beam Radiation Therapy Before Surgery for Patients With Esophageal Adenocarcinoma

2011 ◽  
Vol 29 (34) ◽  
pp. 4555-4560 ◽  
Author(s):  
Lawrence P. Leichman ◽  
Bryan H. Goldman ◽  
Pierre O. Bohanes ◽  
Heinz J. Lenz ◽  
Charles R. Thomas ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Neoadjuvant Therapy ◽  
Esophageal Adenocarcinoma ◽  
Phase Ii ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
External Beam Radiation Therapy ◽  
External Beam Radiation ◽  
External Beam ◽  
Beam Radiation

Purpose Pathologic complete response (pCR) after neoadjuvant therapy for locally advanced esophageal adenocarcinoma is associated with improved survival. The Southwest Oncology Group designed a trimodality, phase II, single-arm trial with objectives of achieving a pCR rate of 40% with prospective exploratory analyses of intratumoral molecular markers postulated to affect response and survival. Patients and Methods Patients with clinically staged II or III esophageal adenocarcinoma received oxaliplatin 85 mg/m2 on days 1, 15, and 29; protracted-infusion fluorouracil (PI-FU) 180 mg/m2/d on days 8 through 43; and external-beam radiation therapy (EBRT) 5 days a week at 1.8 Gy/d for 25 fractions; surgery was performed 28 to 42 days after neoadjuvant therapy. Chemotherapy was planned after surgery. Tumors were analyzed for mRNA expression and polymorphisms in genes involved in drug metabolism and DNA repair. Results Ninety-three patients were evaluable. Two deaths (2.2%) were attributable to preoperative therapy, and two deaths (2.2%) were attributable to surgery. Grade 3 and 4 toxicities were recorded for 47.3% and 19.4% of patients, respectively. Seventy-nine patients (84.9%) underwent surgery; 67.7% of patients had R0 resections. Twenty-six patients (28.0%) had confirmed pCR (95% CI, 19.1% to 38.2%). At a median follow-up of 39.2 months, estimates of median and 3-year overall survival (OS) were 28.3 months and 45.1%, respectively. Intratumoral ERCC-1 gene expression was inversely related to progression-free survival and OS. Conclusion Neoadjuvant oxaliplatin, PI-FU, and EBRT for esophageal adenocarcinoma is active and tolerable. Because the regimen failed to meet the primary end point, it does not define a new standard. However, future trials can be built on this platform to validate the role of ERCC-1 in determining the best systemic regimen for individual patients.

A phase I study of erlotinib, bevacizumab, and external beam radiation therapy (RT) for patients with localized pancreatic carcinoma (PC).

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 281-281 ◽  
Author(s):  
B. G. Czito ◽  
C. Willett ◽  
P. Kennedy-Newton ◽  
D. S. Tyler ◽  
H. Hurwitz ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Phase I ◽  
Dose Level ◽  
Phase Ii ◽  
Phase I Study ◽  
Locally Advanced ◽  
Exploratory Laparotomy ◽  
External Beam Radiation ◽  
Beam Radiation ◽  
Level 1

281 Background: Localized PC is commonly managed with chemoradiotherapy, with or without surgical resection. The optimal combination of agents and doses is the subject of continued investigation. This phase I study examines the combination of two targeted radiosensitizing agents in combination with radiation therapy. Methods: Eligible patients had resectable, borderline resectable or locally advanced adenocarcinoma. Patients received RT (1.8 Gy qd to 50.4 Gy) concurrent with bevacizumab and erlotinib. Dose-level 1 was bevacizumab 10 mg/kg weeks 1, 3 and 5 and erlotinib 100 mg daily, RT days only. Drug doses were escalated depending on encountered toxicity. The primary endpoint was determination of the maximally tolerated dose of this combination. Secondary endpoints included toxicity and activity assessment. Results: Nine patients were enrolled in the phase I study. Maximal EUS/CT stage was T2N0 (n=1), T3N0 (n=1), T3N1 (n=2) or T4N0 (n=5). Of 3 patients in dose-level 1, two had radiographic stable disease (SD) and one partial response (PR). One pt underwent exploratory laparotomy and found to be unresectable, experiencing prolonged postoperative incisional healing. Three patients were then enrolled at dose-level 2 (bevacizumab 10 mg/kg, erlotinib 125 mg). Two had SD and one progressive disease (PD). One pt underwent exploratory laparotomy, aborted due to previously undetected hepatic metastases. Three patients were then enrolled at dose-level 3 (bevacizumab 10 mg/kg, erlotinib 150 mg). One pt had SD and two PR. One pt underwent distal pancreatectomy, experiencing postoperative pancreatic leak and abscess formation. All patients with elevated CA 19-9 at baseline had a decrease, with amedian decrease of 69% (R:13-93%). Dose-limiting toxicity (DLT) was not encountered at any dose-level. Primary non-dose limiting toxicities in all cohorts included NCI CTCAE v3.0 grade 1-2 nausea/vomiting, rash, diarrhea, fatigue, and anorexia. Conclusions: Concurrent chemoradiotherapy utilizing erlotinib and bevacizumab is reasonably well-tolerated. The recommended phase II dose is bevacizumab 10 mg/kg weeks 1, 3, and 5 and erlotinib 150 mg RT days only. Phase II accrual is underway. [Table: see text]

Comparing intensity modulated radiotherapy and conventional external beam radiotherapy in cervical cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 5610-5610
Author(s):  
Deleep Kumar Gudipudi ◽  
Krishnam Raju Alluri ◽  
Maria B. De Leon ◽  
Higinia Rosa Cardenes ◽  
Giuseppe Del Priore
Keyword(s):  
Cervical Cancer ◽  
Radiation Therapy ◽  
Side Effects ◽  
External Beam Radiation ◽  
External Beam ◽  
Beam Radiation ◽  
Skin Reactions ◽  
Intensity Modulated ◽  
Acute Side Effects

5610 Background: To compare Intensity-modulated radiation therapy (IMRT) with conventional external beam radiation therapy (CXRT) regarding morbidity, tumor response, and quality of life (QOL) in cervical cancer patients. Methods: Between 8/2009-2/2010, 50 patients (pts) with age range 20-85, with FIGO Stage IIA- IIIB were prospectively randomized 2:1 to CXRT and IMRT at Indo-American Cancer Institute. Both groups received concurrent chemotherapy (weekly cisplatin 30-40mg/m2) with external beam radiation (EBRT), 50Gy/25fractions followed by intracavitary brachytherapy at 21Gy/3fractions. Complications and QOL were evaluated during treatment and in follow-up with CTC 4.0 and EORTC QLQ-C30, and disease recurrence was based on pelvic exam. Analysis used Chi square(X2) at a significance level of 0.05. Results: Average time to completion was 49 and 48 days in CXRT and IMRT arms (p>.05). Four pts did not complete the treatment in the CXRT. Two months after completion 31/35 (89%) of CXRT and 15/15 (100%) of IMRT had complete response (p>.05). At 5 months, 30/35 (86%) of CXRT, and 14/15 (100%) of IMRT had no loco-regional disease (LRD); 1 IMRT pt died from distant metastasis (DM). At 18 months, 25/35 (72%) in CXRT and 14/15 (93.5%) in IMRT had no LRD or DM. Most common acute side effects in the CXRT were Grade 1 vomiting/cystitis/diarrhea and Grade 2 nausea/skin reactions/proctitis. One pt developed vesicovaginal fistula (VVF) after 50Gy by EBRT. Most common acute side effects in the IMRT were Grade1 nausea/vomiting/cystitis/proctitis/diarrhea. Two pts had grade 3 neutropenia in the 5th week of RT. QOL was better in IMRT (p <.01) based on functional, symptom, single items, and global scales except for pain, insomnia, loss of appetite. Diarrhea, financial problems were worse in the CXRT (p<.05). Chronic complications such as radiation induced proctitis in 5 patients, and sub-acute intestinal obstruction in 2 patients during follow-up period in CXRT vs. IMRT (p < 0.001). Conclusions: IMRT is superior to CXRT with fewer chronic side effects and similar acute side effects and treatment responses. This is the first randomized clinical trial of these treatments in cervical cancer.

Intratumoral chemotherapy as an adjunct to endobronchial brachytherapy

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 7591-7591
Author(s):  
D. Nader ◽  
P. Ketterl ◽  
D. Kelly ◽  
J. Flynn ◽  
J. J. Stark ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Radiation Therapy ◽  
Locally Advanced ◽  
External Beam Radiation ◽  
Normal Lung ◽  
Tumor Control ◽  
Beam Radiation ◽  
Nsclc Patients ◽  
The Impact

7591 Background: NSCLC patients (pts) with clinically significant endobronchial obstruction have a poor prognosis and quality of life in both locally advanced and metastatic stages of disease. Radiation therapy (RTx) in conjunction with chemotherapy (CTx) improves survival compared to either modality alone but produces greater toxicity and morbidity. Significant clinical benefit with respect to disease management and quality of life could be realized with improved methods for controlling obstructing endobronchial lesions. The hypothesis for this study is that optimal clinical control of endobronchial lesions can be achieved by intratumoral injection of a drug with both clinical activity against NSCLC and synergy with RTx. Cisplatin (CPt), an active agent in NSCLC and a known radiosensitizer is an ideal drug for this objective. Thus, the goal of this exploratory study was to determine the clinical efficacy and tolerance to intratumoral CPt injection in combination with HDR brachytherapy (BTx) in NSCLC patients with obstructing endobronchial lesions. Methods: NSCLC pts (n=16) with > 75% endoluminal obstruction of a main or lobar airway were evaluated. Intratumoral CTx consisted of CPt (1 mg/ml; 0.5–2.0 ml/session) injected into the entire visible tumor through a flexible 21 gauge needle through the bronchoscope. BTx was given as 500 cGy/session at one cm diameter for 4 sessions concomitant with CTx. Results: All pts completed the entire 4 sessions of planned local therapy. There was complete resolution of injected lesions in 14/16 pts confirmed bronchoscopically and cytologically. In the other 2 pts, necrotic tissue occupying < 10 and 20% of the airway, cytologically negative for tumor was seen. There were no adverse events or complications related to bronchoscopy or local CTx. Conclusions: The results of this study demonstrate that intratumoral administration of CPt, as an adjunct to endobronchial BTx for the management of endobronchial obstructing lesions in patients with NSCLC is safe and effective. This approach offers the possibility of superior local tumor control while reducing toxicity to normal lung and esophagus as compared to conventional external beam radiation therapy modalities. Further studies evaluating the impact of this approach on survival and quality of life are warranted. No significant financial relationships to disclose.

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