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Background/aim: To evaluate the outcome and toxicities in patients with locally advanced cervical cancer (LACC) treated with radiochemotherapy and intracavitary brachytherapy., Patients and Methods: This study included 67 patients with LACC treated between 2010 and 2018. The most represented stage was FIGO IIB. The patients were treated with external beam radiotherapy (EBRT) to the pelvis and boost to the cervix and parametrials. Concomitant chemotherapy (CHT) with cisplatin (CDDP) 40 mg/mq was planned. Subsequently, the patients underwent CT-based endouterine brachytherapy (BT). The response was evaluated at 3 months with PET-CT and/or pelvic magnetic resonance imaging (MRI). Since then, the patients have been followed with clinical instrumental controls every 4 months for the first 2 years and every 6 months for the following 3 years. Local response was assessed with pelvic MRI and/or PET-CT scan at the end of intracavitary BT) according to RECIST 1.1 criteria., Results: The median duration of treatment was 55 days (range=40-73 days). The prescription dose to the planning target volume (PTV) was delivered in 25 to 30 (median 28) daily fractions. The EBRT median dose to the pelvis and gross tumor volume were 50.4 Gy (range=45-56.25) and 61.6 Gy (range=45-70.4), respectively. The 1-year, 2-year, 3-year, and 5-year overall survival rates were 92.44%, 80.81%, 78.84%, and 76.45% respectively. The actuarial 1-year, 2-year, 3-year, and 5-year disease-free survival rates were 89.5%, 83.6%, 81%, and 78.2% respectively., Conclusion: This study analyzed acute and chronic toxicity, survival, and local control in cervical cancer patients treated with IMRT followed by CT-planned high dose rate-brachytherapy. Patients demonstrated satisfactory outcomes and incidence of acute and late toxicities., Competing Interests: The Authors have no conflicts of interest to declare in relation to this study., (Copyright 2023, International Institute of Anticancer Research.)

Background/aim: We evaluated local control and toxicity in patients receiving radiotherapy associated with immune check point inhibitors and analyzed which oligometastatic disease setting benefits the most from local ablation in terms of advantage in overall survival., Patients and Methods: We retrospectively identified 60 oligoprogressive patients treated with a PD-1 inhibitor in association with radiotherapy on the site of progression (119 lesions)., Results: After a median follow-up of 11.7 months (range=1-39 months), we observed complete response (CR) in 45/119, partial response (RP) in 42/119, and stable disease (SD) in 30/119 patients. Nine radionecrotic events occurred. Two patients experienced grade 3 toxicities and 32 patients reported grade 2 toxicities. The number of radiologically evident metastatic organs in patients who received concomitant PD-1 inhibitors and radiotherapy showed a significant increase in survival (respectively, 73% after 12 months and 47% after 24 months) in patients with 0-3 metastatic organs compared to those with more than 3 organ sites involved (p<0.0001)., Conclusion: Radiotherapy associated with PD-1 inhibitors is overall safe and efficacious. Patients eligible for intensification of local treatments should have less or equal to 3 metastatic organ sites., (Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Standard treatment for locally advanced cervical cancer is external beam radiotherapy followed by brachytherapy (BT). Stereotactic body radiation therapy (SBRT) is a possible option for treating patients ineligible for BT., Patients and Methods: From October 2012 to July 2020, nine women with cervical cancer received SBRT to high-risk volumes. The Kaplan-Meier method was used to estimate the rates of overall and disease-free survival., Results: The median age was 52 years; 88% of patients had squamous carcinoma. Reasons for forgoing BT were cervical canal stenosis, treatment refusal and hematological disease. The median boost dose was 18 Gy and the median dose per fraction was 6 Gy. Median follow-up was 16 months. The median survival was 24 months, the actuarial 2-year OS rate was 70%, and median disease-free survival was 11 months. One grade 3 late vaginal toxicity was reported. No acute nor late grade 4 toxicities were observed., Conclusion: SBRT boost in patients with cervical cancer ineligible for BT led to acceptable survival outcomes and a safe toxicity profile., Competing Interests: The Authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article., (Copyright 2021, International Institute of Anticancer Research.)

Aim: To evaluate the efficacy of residual site radiation therapy (RSRT) on local control (LC), progression-free (PFS) and overall (OS) survival in patients with primary mediastinal lymphoma (PMBCL), following rituximab and chemotherapy treatment (ICHT)., Patients and Methods: The study included 34 patients with PMBCL treated between 2006 and 2014 with ICHT with/without autologous stem cell transplantation and RSRT. Between the end of ICHT/stem cell transplantation and RSRT, patients were evaluated with 18 F-fluorodeoxyglucose positron-emission tomography. The gross tumor volume included morphological mediastinal residual disease after ICHT/SCT. The percentage of LC, PFS and OS were assessed., Results: All patients received RSRT with a median dose of 30 Gy. Median follow-up was 82 months. One patient out of 34 (3%) showed progressive disease 9 months from diagnosis. The 10-year PFS and OS were 97% and 97% respectively., Conclusion: RSRT in patients with PMBCL treated with ICHT did not impact unfavorably on LC and patient survival., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Oropharyngeal mucositis occurs in virtually all patients with head and neck cancer receiving radiochemotherapy. The manipulation of the oral cavity microbiota represents an intriguing and challenging target., Patients and Methods: A total of 75 patients were enrolled to receive Lactobacillus brevis CD2 lozenges or oral care regimen with sodium bicarbonate mouthwashes. The primary endpoint was the incidence of grade 3 or 4 oropharyngeal mucositis during radiotherapy treatment., Results: There was no statistical difference in the incidence of grade 3-4 oropharyngeal mucositis between the intervention and control groups (40.6% vs. 41.6% respectively, p=0.974). The incidence of pain, dysphagia, body weight loss and quality of life were not different between the experimental and standard arm., Conclusion: Our study was not able to demonstrate the efficacy of L. brevis CD2 lozenges in preventing radiation-induced mucositis in patients with head and neck cancer. Although modulating homeostasis of the salivary microbiota in the oral cavity seems attractive, it clearly needs further study., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: To evaluate outcomes in patients with low-risk prostate cancer treated with hypofractionated radiotherapy (HyRT)., Patients and Methods: Between April 2004 and December 2015, 175 patients with low-risk prostate cancer were treated with HyRT 60 Gy in 20 fractions with or without image guidance and reduction of margin from clinical target volume to planning target volume., Results: The median follow-up was 66 months. The 8-year overall survival for the whole patient cohort was 88.9%. The 8-year biochemical no evidence of disease was higher in patients treated with image-guided HyRT (98.8% vs. 88%, p=0.023). During treatment, patients treated with image-guided HyRT presented a lower rate of grade 1-2 gastrointestinal toxicity (25.3% vs. 42.2%, p=0.001). At the last follow-up, the grade 1 Gastro-intestinal toxicity rate was 4.0% and the grade 1-2 genito-urinary toxicity rate was 25.1%., Conclusion: Our study demonstrated the efficacy of the schedule used with a low rate of acute and late toxicities. Therefore, reduction of margins with image-guided HyRT is safe., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Epithelial skin cancer frequently occurs in the elderly population, sometimes in an advanced stage, when intensive treatments are needed. Radiotherapy can achieve high response rates. We evaluated efficacy and tolerability of hypofractionated radiotherapy in a population of very elderly patients with locally advanced epithelial skin cancer., Patients and Methods: Two different hypofractionated schedules were administered (21 patients): 6 Gy in 10 bi-weekly fractions (13 lesions) and 5 Gy in 12 bi-weekly fractions (13 lesions). Median age at treatment was 88 years, life expectancy was ≤5 years in 90.5%., Results: The overall response rate was 96.1%, with 92.4% complete responses. All patients experienced an improvement of their symptoms and a reduction of pain and medication. The median overall survival time was 28 months (95% confidence interval=4.7-51.2 months). At the time of analysis, 52.3% of patients had died., Conclusion: Hypofractionated radiotherapy is an effective option of treatment, with low toxicity and optimal results, and can also be safely administered to these frail patients., (Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Aim: Stage IV non-small cell lung cancer (NSCLC) is characterized by poor prognosis. Palliative chemotherapy and/or best supportive care are considered standard treatment. Nevertheless, for patients with limited distant metastases (1-5 metastases), called oligometastatic disease, better prognosis has been observed. We evaluated response rate, survival, time to progression and toxicity in oligometastatic/oligorecurrent NSCLC patients treated with stereotactic body radiotherapy (SBRT) delivered to all active sites in the lung., Patients and Methods: Twenty-nine lung metastases in 22 patients affected by oligometastatic/oligorecurrent NSCLC were treated with SBRT to all active sites of disease. Inclusion criteria were: controlled primary tumor with complete response or stable disease after surgery/radiotherapy/combined therapy; ≤4 synchronous or metachronous lung metastases at the time of treatment; no other active sites of distant metastases., Results: Response to treatment was as follows: complete response in 21% of lesions, partial response in 69% of metastases, stable disease in 10%. Ninenty-one percent of patients had complete metabolic response, and 9% had a partial metabolic response. Median follow-up was 18 months. The 1-year and 2-year OS was 86% and 49%, respectively. The 1-year and 2-year PFS was 79% and 40%, respectively. Median time to progression and median OS were 18 months and 24 months, respectively. Local control was 93% at 1 year and 64% at 2 years. Overall, acute toxicity occurred in 18% (4/22) of patients; two patients experienced grade 2 pneumonitis. Grade ≤2 late toxicity occurred in 50% of patients. No grade ≥3 toxicities were recorded., Conclusion: Aggressive stereotactic radiotherapy is a feasible and well-tolerated treatment for oligometastatic/oligorrecurrent NSCLC patients with lung metastases offering longer survival. Ablative radio therapy has a potential role in the management of well-selected stage IV NSCLC patients while increasing their quality of life and survival., (Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Background: We conducted long-term follow-up analysis of the outcomes for patients affected by advanced-stage non-small cell lung cancer (NSCLC) treated with hypofractionated radiotherapy (RT)., Materials and Methods: Sixty patients with advanced-stage NSCLC (IIIA-IV) treated with hypofractionated radiotherapy (60Gy/20 fractions) were analyzed. Radiation was delivered using an image-guided RT technique to verify the correct position. Toxicities were graded according to the Common Toxicity Criteria for Adverse Effects v4.0 scale., Results: Overall, six patients achieved a complete response and 46 patients had a partial response (tumor response rate 86%). After a median follow-up of 30 months, locoregional progression occurred in 23 patients and distant progression occurred in 38. The 1-year and 2-years overall survival were 57% and 40%, respectively. The 1-year and 2-years progression-free survival (PFS) were 47.1% and 33.5%, respectively. The median duration of OS and PFS was 13 months and 12 months, respectively. The 2-year local PFS and metastases-free survival (MFS) were 53% and 40.3%, respectively. On univariate analysis, the T-size (≥5 cm), and type of response to RT (non-response/progressive disease) were significantly associated with worse OS. Type of response was identified as significant prognostic factors for PFS (p<0.01) local PFS (p=0.015) and MFS (p<0.01). Acute grade 3 esophagitis and pneumonitis occurred in three patients (5%) and four patients (6%), respectively. Late grade 3 esophagitis and pneumonitis occurred in 2% (one patient) and 3% (two patients), respectively. No patient experienced grade 4 acute or late RT-related toxicities., Conclusion: Hypofractionated RT offers good disease control for patients with advanced-stage NSCLC with acceptable toxicity rates. Phase III randomized trials are necessary to compare hypofractionated RT with conventional RT., (Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Aim: To evaluate survival and toxicity in a cohort of patients treated with stereotactic body radiation therapy (SBRT) for unresectable intrahepatic malignancies., Patients and Methods: From 2007 to 2014, 23 patients with 34 lesions (three primary and 31 metastatic liver tumors) were treated with SBRT., Results: The median follow-up was 9 months (range=1-76) for all patients. Local control was reached in 27 out of 34 (79%) treated lesions, with 1 and 2 years rates of 93% and 73%, respectively. The progression-free survival at 1-year and 2-year was 50% and 25%, respectively. Median overall survival was 16 months (95% confidence interval=8-24 months), with 1-year and 2-year rates of 58% and 41%, respectively. Toxicity was very low consisting mainly of grade 1 and 2 events., Conclusion: SBRT provides good local control for both primary and metastatic liver lesions, with minimal toxicity., (Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Aim: This is a retrospective analysis of a selected series of high-risk non-small cell lung cancer (NSCLC) patients with post-surgical loco-regional relapse treated with salvage stereotactic body radiotherapy (SBRT). Outcome and toxicity profiles were assessed., Patients and Methods: Twenty-eight patients (unfit for surgery or systemic therapy) with 30 lesions underwent salvage SBRT as an alternative therapy because of advanced age, co-morbid conditions or no response obtained from other treatments., Results: Complete and partial responses were 16% and 70%, respectively. Local progression was observed in 3 patients. Regional relapse occurred in 5 patients. Distant progression occurred in 10 patients. The 2-year overall survival (OS) and disease-free survival (DFS) were 57.5% and 36.6%, respectively. Radiation acute pneumonitis occurred as follows: three patients developed grade 1, two patients experienced grade 2 and one patient experienced grade 3 toxicity., Conclusion: Stereotactic body radiotherapy could have an alternative role in isolated loco-regional relapse in patients unfit or resistant to other therapies., (Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Aim: To evaluate the effectiveness of intra-operative radiotherapy (IORT) in breast cancer in terms of local control, esthetic results and disease-free survival., Patients and Methods: From June 2007 to October 2011, 110 patients with early-stage breast cancer were submitted to quadrantectomy and IORT. A total dose of 21 Gy prescribed at 90-100% isodose was delivered in all cases. Patients were evaluated after surgery for early and late complications., Results: Median follow-up was 27 (range: 2-54) months. In 10 patients (9.1%), breast ultrasound showed liponecrosis. Six patients (5.5%) developed grade 2 fibrosis. Disease-free survival rates at 2 and 3 years were 96.8% and 92.9 %. Three patients (2.7%) developed local recurrence, two patients (1.8%) distant metastasis. Two patients died. The 2- and 3-year overall survival rates were 100% and 97.3%, respectively., Conclusion: IORT could be an appropriate therapeutic alternative in selected patients although it remains investigational; longer follow-up to confirm these results is required.

Vaginal intraepithelial neoplasia (VaIN) represents a rare and asymptomatic pre-neoplastic lesion. Its natural history and potential evolution into invasive cancer are uncertain. VaIN can occur alone or as a synchronous or metachronous lesion with cervical and vulvar HPV-related intra epithelial or invasive neoplasia. Its association with cervical intraepithelial neoplasia is found in 65% of cases, with vulvar intraepithelial neoplasia in 10% of cases, while for others, the association with concomitant cervical or vulvar intraepithelial neoplasias is found in 30-80% of cases. VaIN is often asymptomatic and its diagnosis is suspected in cases of abnormal cytology, followed by colposcopy and colposcopically-guided biopsy of suspicious areas. In the past, high-grade VaIN and multifocal VaIN have been treated by radical surgery, such as total or partial upper vaginectomy associated with hysterectomy and radiotherapy. The need to maintain the integrity of reproductive capacity has determined the transition from radical therapies to conservative ones, according to the different patients' characteristics.

Aim: To evaluate outcome and prognostic factors in patients with locally advanced gastric cancer., Patients and Methods: From 2007 to 2011, 55 patients underwent adjuvant radiotherapy and concurrent chemotherapy with 5-fluorouracil (64%) or capecitabine (36%). D2 node resection was performed in all patients. The pathological stage was as follows: 13% IB; 29% II; 24% IIIA; 9% IIIB and 25% stage IV., Results: The median follow up was 21 months. Five-years overall and disease-free survival were 44.5% and 48%, respectively. Eighteen patients experienced disease relapse after combined treatment; in five of these patients, relapse was both locoregional and systemic. The most common toxicity was grade 1-2 leukopenia, reported in 32% of cases. Six patients developed grade 3 toxicity. Nodal ratio ≥0.4 and N3 stage were significant prognostic factors for survival and relapse., Conclusion: Adjuvant conformal radiotherapy and concurrent chemotherapy is a feasible and well-tolerated treatment for patients with locally advanced gastric cancer.

Background: To evaluate the acute tolerance to hypofractionated schedule of patients with prostate cancer., Patients and Methods: We treated 62 patients with intermediate risk prostate cancer. All patients were treated with a total dose of 43.8 Gy on seminal vesicles and 54.75 Gy on prostate, 3.65 Gy per fraction, three times a week for a total of 5 weeks. All patients underwent neoadjuvant, concomitant and adjuvant hormonal therapy. Thirty-six patients were submitted to image-guided radiation therapy (IGRT)., Results: Median follow-up was 15 months (range 3-33 months). Toxicities during the treatment were: grade 1-2 gastrointestinal (GI) toxicity, 22.6%; grade 1-2 genitourinary (GU) toxicity, 51.6%. Toxicities 3 months after the end of the treatment were grade 1-2 GI 6.5%, grade 1-2 GU 9.7%. No statistical difference was observed comparing acute toxicity in patients treated with or without IGRT., Conclusion: This study showed that the hypofractionation schedule used is well tolerated, with a low rate of acute grade 1-2 GI toxicity and without major grade (≥3) acute toxicity. Longer follow-up is needed to determine if this low rate of acute toxicity will be translated in a low rate of late toxicity.

Background: The treatment of primary cutaneous lymphoma is still ongoing and the role of radiotherapy, as exclusive or combined modality, is not yet clear., Materials and Methods: From 1994 to June 2004, 29 patients with cutaneous B-cell lymphoma and 9 patients with cutaneous T-cell lymphoma were treated by radiotherapy (median dose of 3900 cGy, range 600-4600 cGy). Eight patients had previously received chemotherapy., Results: The complete response rate was 94.7% with progressive disease in two patients (5%). Sixteen (42.1%) patients relapsed, with the relapse occurring only in the skin site as single episode (9 patients) and more than two episodes (7 patients). The 5-year overall survival and event-free survival were 94% and 53%, respectively., Conclusion: Radiotherapy offers a substantial local control of primary cutaneous lymphoma, both as exclusive or combined approach. The patients with wide-spread or multiple lesions, usually candidates for radiotherapy and chemotherapy, are amenable to radiotherapy alone.

Background: To improve long-term survival by reducing toxicity in intermediate stage Hodgkin's disease patients, we compared the effects of involved field (IF) versus extended field (EF) irradiation administered after four cycles of ABVD regimen., Materials and Methods: Two hundred and ten Hodgkin's disease patients, at clinical stage II with risk factors and III without risk factors, were enrolled in the randomized study HD94. After four courses of ABVD regimen, patients who achieved complete remission (CR) or partial remission (PR) were randomly assigned to the IF or EF arm. The Kaplan-Meier method was adopted to estimate overall survival (OS) and relapse-free survival (RFS)., Results: After a median follow-up of 78 months (range 13-111 months), OS was 98% and 96%, respectively, in the EF and IF arms; RFS was 94% and 91%, respectively, in the EF and IF arms., Conclusion: We confirm the efficacy of four cycles of ABVD regimen, with suitable dose intensity, and radiotherapy as consolidation therapy, in intermediate stage Hodgkin's disease patients (CR = 99.5% and OS = 95%). We also found that involved field radiotherapy results were as effective as extended field, without acute toxicity.

Background: A randomized trial was conducted to determine (a) the role of radiotherapy and chemotherapy on local control and (b) to determine the timing of radiotherapy for early-stage breast cancer., Materials and Methods: Five hundred and ninety patients were treated with both conservative surgery and radiotherapy (group A). The average time interval between surgery and radiation was 90 days for 452 patients and over 90 days for 138 patients. One hundred and ninety-four patients underwent adjuvant therapy based on CMF regimens (group B)., Results: Among 396 patients of group A, 8.1% had local failure; we observed 7.2% local recurrences in 363 patients who received therapy before 90 days and 18.2% in patients who received therapy after 90 days. Among patients of group B, 7.7% had local failure; for patients who underwent radiotherapy before 90 days, the local recurrence rate was 6.6%, compared with 12.3% for patients who underwent therapy more than 90 days after surgery., Conclusion: In patients who are eligible to receive chemotherapy, it is possible to administer radiotherapy after systemic treatment, while in patients who have to be treated with radiotherapy more then 90 days after breast surgery, chemotherapy can reduce the local failure rate.

Background: A brief course of chemotherapy followed by radiation therapy was considered the best treatment for localized high-grade Non-Hodgkin's Lymphoma (NHL). The purpose of this study was to determine the efficacy and feasibility of a brief-course of anthracycline-based chemotherapy (CHOP) and consolidation radiation therapy (CRT) in a series of 57 consecutive patients with stage I-IE intermediate-high grade NHL., Patients and Methods: Between January 1990 and December 1998, 57 consecutive patients, stage I=31 (55%) and stage IE=26 (45%), were treated with 3 cycles of CHOP regimen. Forty-four (77%) received a CRT and thirteen (23%) with primitive gastric and splenic NHL underwent radical surgery. Multivariate analysis was performed to evaluate age, lactate dehydrogenase (LDH), bulky, nodal versus extranodal localization, as prognostic factors of locoregional control and survival., Results: After a median follow-up of 84 months (range 4-128 months) the 5-year overall survival (OS), disease-free survival (DFS) and event-free survival (EFS) rates were 88%, 87.5% and 84%, respectively. Risk factor analysis revealed that the LDH value was the most important adverse prognostic factor for OS and EFS. No differences were found regarding the age and or extranodal localization. The 5-year OS, DFS and EFS was 100% in thirteen patients with primitive gastric or splenic NHL treated with a radical surgical approach followed by chemotherapy without CRT., Conclusion: We confirm the efficacy and feasibility of a brief course of CHOP chemotherapy followed by CRT in localized I-IE intermediate-high grade NHL without adverse prognostic factors. Randomized studies are warranted in order to define the dose and the target volume of CRT (involved field or extended field) in this setting of patients.

Background: The best treatment of Nasopharyngeal Carcinoma (NPC) is still an open question. The purpose of this retrospective study was to determine risk factors that affect locoregional control and treatment outcome of NPC patients after radiotherapy, with or without chemotherapy., Methods: Between January 1976 and December 1996, 66 consecutive patients (stage I = 0; stage II = 13; stage III = 32; stage IV = 21) were given definitive radiotherapy at a single Institution. Concurrent or adjuvant chemotherapy was also given to 14 of them (21%). Multivariate analysis was performed to evaluate age, T stage, N stage, radiotherapy dose, histology, chemotherapy bone of skull erosions or cranial nerve palsies and base of skull involvement as prognostic factors of locoregional control and overall survival., Results: By the end of January 2000, after a median follow-up of 66 months and a minimal follow-up of 36 months, the event-free overall survival rate of 5 years was 48% and the overall survival 54%. Risk factor analysis revealed that radiotherapy dose, age and stage were the most important factors for overall survival of these patients. The 5 year overall survival was 89% for stage II and 49% for stage III-IV (p = 0.004), 62% for dose higher than 60 Gy and 20% for dose below 60 Gy (p = 0.007), 62% for age below 65 years and 36% for age higher than 65 years (p = 0.027). The concurrent or adjuvant chemotherapy did not have prognostic significance., Conclusions: We confirm the need to determine the risk factors in patients with NPC. The choice of treatment, whether radiotherapy alone, at dose > 60 Gy, or radiotherapy plus chemotherapy, should be made after identification of patients with high risk disease, suitable for the combined modality.

A simple semi-automated apparatus is described for rinsing the transport line from the [18F] fluoride. target to the hot-cell after recovery of aqueous [18F] fluoride. The additional activity thus recovered can then be added to that previously trapped on Dowex 1X8 (CO3=) or, alternatively, diverted to a second vial for other uses such as research, PET-camera calibration or bone investigations by PET. Inclusion of the target chamber in the rinsing procedure increased the additional recovery of activity up to ca. 15%, without a noticeable effect on the isotopic integrity of the recovered [18O]H2O.