AIRO Breast Cancer Group Best Clinical Practice 2022 Update.

INTRODUCTION: Breast cancer is the most common tumor in women and represents the leading cause of cancer death. Radiation therapy plays a key-role in the treatment of all breast cancer stages. Therefore, the adoption of evidence-based treatments is warranted, to ensure equity of access and standardization of care in clinical practice. METHOD: This national document on the highest evidence-based available data was developed and endorsed by the Italian Association of Radiation and Clinical Oncology (AIRO) Breast Cancer Group.We analyzed literature data regarding breast radiation therapy, using the SIGN (Scottish Intercollegiate Guidelines Network) methodology (www.sign.ac.uk). Updated findings from the literature were examined, including the highest levels of evidence (meta-analyses, randomized trials, and international guidelines) with a significant impact on clinical practice. The document deals with the role of radiation therapy in the treatment of primary breast cancer, local relapse, and metastatic disease, with focus on diagnosis, staging, local and systemic therapies, and follow up. Information is given on indications, techniques, total doses, and fractionations. RESULTS: An extensive literature review from 2013 to 2021 was performed. The work was organized according to a general index of different topics and most chapters included individual questions and, when possible, synoptic and summary tables. Indications for radiation therapy in breast cancer were examined and integrated with other oncological treatments. A total of 50 questions were analyzed and answered.Four large areas of interest were investigated: (1) general strategy (multidisciplinary approach, contraindications, preliminary assessments, staging and management of patients with electronic devices); (2) systemic therapy (primary, adjuvant, in metastatic setting); (3) clinical aspects (invasive, non-invasive and micro-invasive carcinoma; particular situations such as young and elderly patients, breast cancer in males and cancer during pregnancy; follow up with possible acute and late toxicities; loco-regional relapse and metastatic disease); (4) technical aspects (radiation after conservative surgery or mastectomy, indications for boost, lymph node radiotherapy and partial breast irradiation).Appendixes about tumor bed boost and breast and lymph nodes contouring were implemented, including a dedicated web application. The scientific work was reviewed and validated by an expert group of breast cancer key-opinion leaders. CONCLUSIONS: Optimal breast cancer management requires a multidisciplinary approach sharing therapeutic strategies with the other involved specialists and the patient, within a coordinated and dedicated clinical path. In recent years, the high-level quality radiation therapy has shown a significant impact on local control and survival of breast cancer patients. Therefore, it is necessary to offer and guarantee accurate treatments according to the best standards of evidence-based medicine.

The Assisi Think Tank Meeting Breast Large Database for Standardized Data Collection in Breast Cancer-ATTM.BLADE.

Background: During the 2016 Assisi Think Tank Meeting (ATTM) on breast cancer, the panel of experts proposed developing a validated system, based on rapid learning health care (RLHC) principles, to standardize inter-center data collection and promote personalized treatments for breast cancer. Material and Methods: The seven-step Breast LArge DatabasE (BLADE) project included data collection, analysis, application, and evaluation on a data-sharing platform. The multidisciplinary team developed a consensus-based ontology of validated variables with over 80% agreement. This English-language ontology constituted a breast cancer library with seven knowledge domains: baseline, primary systemic therapy, surgery, adjuvant systemic therapies, radiation therapy, follow-up, and toxicity. The library was uploaded to the BLADE domain. The safety of data encryption and preservation was tested according to General Data Protection Regulation (GDPR) guidelines on data from 15 clinical charts. The system was validated on 64 patients who had undergone post-mastectomy radiation therapy. In October 2018, the BLADE system was approved by the Ethical Committee of Fondazione Policlinico Gemelli IRCCS, Rome, Italy (Protocol No. 0043996/18). Results: From June 2016 to July 2019, the multidisciplinary team completed the work plan. An ontology of 218 validated variables was uploaded to the BLADE domain. The GDPR safety test confirmed encryption and data preservation (on 5000 random cases). All validation benchmarks were met. Conclusion:BLADE is a support system for follow-up and assessment of breast cancer care. To successfully develop and validate it as the first standardized data collection system, multidisciplinary collaboration was crucial in selecting its ontology and knowledge domains. BLADE is suitable for multi-center uploading of retrospective and prospective clinical data, as it ensures anonymity and data privacy.

Oncotype DX Predictive Nomogram for Recurrence Score Output: The Novel System ADAPTED01 Based on Quantitative Immunochemistry Analysis.

PURPOSE: Oncotype DX (ODX) predicts breast cancer recurrence risk, guiding the choice of adjuvant treatment. In many countries, access to the test is not always available. We used correlation between phenotypical tumor characteristics, quantitative classical immunohistochemistry (IHC), and recurrence score (RS) assessed by ODX to develop a decision supporting system for clinical use. PATIENTS AND METHODS: Breast cancer patients who underwent ODX testing between 2014 and 2018 were retrospectively included in the study. The data selected for analysis were age, menopausal status, and pathologic and IHC features. IHC was performed with standardized quantitative methods. The data set was split into two subsets: 70% for the training set and 30% for the internal validation set. Statistically significant features were included in logistic models to predict RS ≤ 25 or ≤ 20. Another set was used for external validation to test reproducibility of prediction models. RESULTS: The internal set included 407 patients. Mean (range) age was 53.7 (31-80) years, and 222 patients (54.55%) were > 50 years old. ODX results showed 67 patients (16.6%) had RS between 0 and 10, 272 patients between 11 and 25 (66.8%), and 68 patients > 26 (16.6%). Logistic regression analysis showed that RS score (for threshold ≤ 25) was significantly associated with estrogen receptor (P = .004), progesterone receptor (P < .0001), and Ki-67 (P < .0001). Generalized linear regression resulted in a model that had an area under the receiver operating characteristic curve (AUC) of 92.2 (sensitivity 84.2%, specificity 80.1%) and that was well calibrated. The external validation set (183 patients) analysis confirmed the model performance, with an AUC of 82.3 and a positive predictive value of 91%. A nomogram was generated for further prospective evaluation to predict RS ≤ 25. CONCLUSION: RS was related to quantitative IHC in patients with RS ≤ 25, with a good performance of the statistical model in both internal and external validation. A nomogram for enhancing clinical approach in a cost-effective manner was developed. Prospective studies must test this application in clinical practice.

Adult Onset Still's Disease and Radiotherapy treatment for breast cancer: Case report about management of this rare association and literature review.

AIM: This manuscript focuses on the first experience in literature of a patient with a complicated Adult Onset Still's Disease-related heart failure who thereafter underwent adjuvant radiotherapy for left breast cancer. BACKGROUND: AOSD is a rare autoimmune inflammation-related disease, in which life-threatening pulmonary and cardiac complications can occur. In literature, AOSD is often associated with cancer, as paraneoplastic syndrome, but there are few data about primary AOSD and management of oncological therapies. MATERIALS AND METHODS: A patient who needed adjuvant breast cancer radiotherapy underwent tumour board evaluation to define feasibility of an RT in a patient with of a history of a heart life-threatening complication 2 years before AOSD. Results of the review were discussed by a multidisciplinary panel of experts that chose the type of surgery, radiotherapy and monitoring of patient. RESULTS: Literature review confirmed association of AOSD with BC in some pts and uniqueness of this treatment management experience. Patient underwent RT according to schedule of 40.05/2.67 Gy/fx on residual left breast and 10/2 Gy/fx on tumour bed with the gating technique. The panel chose to keep immunosuppressive therapy with anakinra. No complications were observed at clinical, ECG and laboratory examinations. Maximum toxicity was G2 skin. At first follow up AOSD signs of flare were negative. CONCLUSION: In conclusion, when oncological treatments, especially radiotherapy, are mandatory for AOSD pts, multidisciplinary management and tailored monitoring are necessary to avoid acute adverse effects and allow pts to complete therapies.

Present clinical practice of breast cancer radiotherapy in Italy: a nationwide survey by the Italian Society of Radiotherapy and Clinical Oncology (AIRO) Breast Group.

AIMS: To investigate the present attitude of the Italian Radiation Oncologists in the management of breast cancer (BC) concerning hypofractionated radiotherapy (hRT), partial-breast irradiation (PBI), re-irradiation (rRT) and radiotherapy after neoadjuvant chemotherapy (post-NAC RT). METHODS: A nationwide, 21-point questionnaire was distributed online via SurveyMonkey. RESULTS: Seventy-four Italian Radiotherapy Centers answered to the survey. In most cases, the responding centers treated more than 100 BC patients/year between January 2016 and December 2017. Almost half of responding centers (49%) treated patients with hRT, out of these, 95% as routine practice for early-stage BC. Dose prescriptions ranged between 39 and 45 Gy indicating a high use of moderate hRT. The chest wall and regional lymph nodes were irradiated with hRT by 13% and 15% of the responding centers, respectively. PBI was used by 60% of responders, with different techniques. Only 0.6% of participants perform rRT after BC recurrence. Finally, only 11% of the interviewed centers responded to their attitude toward post-NAC RT, which, however, was indicated in 97% of patients after breast-conserving surgery. CONCLUSIONS: This survey shows a fairly good use of hRT and a moderate practice of PBI in Italy. Some practices like hRT to the chest wall and regional lymph nodes as well as rRT need further verification. Likewise, the management of post-NAC RT is very heterogeneous. Future national clinical collaborative studies are advocated in order to investigate these controversial topics about breast cancer radiotherapy.

Shoulder girdle impairment in breast cancer survivors: the role of range of motion as predictive factor for dose distribution and clinical outcome.

BACKGROUND: Pain and functional impairment of the ipsilateral shoulder girdle in patients who underwent surgery and radiotherapy for breast cancer (BC) is a late complication reported in the literature. We analyze a correlation with dosimetric parameters and propose an algorithm for sparing strategies. METHODS: A total of 111 patients treated for BC were included in this observational analysis during follow-up protocol visits. Exclusion criteria were the presence of moderate or severe arthrosis history and/or rheumatologic diseases. All the patients had complete physical and multidimensional examinations during joint (physiatrist and radiotherapy oncology) follow-up visits. A scapula-humeral articulation (SHA) standardized contouring was performed retrospectively on Eclipse® treatment plans. A possible correlation between patients' characteristics, radiotherapy, and dosimetry analysis and functional impairment was investigated at statistical analysis. Results of analysis were summarized into a proposal of algorithm for sparing SHA. RESULTS: A total of 111 patients were selected during follow-up visits. Mean age of patients was 60 years (range 41-85 years). A total of 103 patients (93%) underwent conservative surgery, with 110 patients (99%) undergoing axilla surgery as well. Fifty-two patients (46.8%) presented a reduction of range of motion (ROM) abduction on the treated side at the observational analysis. Mean ROM abduction reduction was 13°06' (range 0°-100°). Disability of the Arm, Shoulder and Hand questionnaire (DASH) score results were excellent in 79 patients (71.2%), discrete in 15 patients (13.5%), good in 15 patients (13.5%), and sufficient in 2 patients (1.8%). Median EQD2 Dmax at SHA was 18 Gy (range 0.22-51.9 Gy) and median EQD2 mean dose at SHA was 2 Gy (range 0.04-24.32 Gy). Univariate analysis showed a linear correlation between DASH score and ROM of abduction of treated side (ρ=-0.7), ROM of abduction and ROM of flexion in ipsilateral arm (ρ=0.8), or ROM of abduction and ROM of flexion in contralateral arm (ρ=0.8). A statistically significant difference in ROM abduction between the 2 arms was found at χ2 test (P<0.05 at χ2 confidence interval = 95%). Cox linear regression analysis showed ROM abduction on treated arm as a predictive factor of DASH score (P<0.0001). Age (P<0.05), DASH score (P=0.006), and ROM abduction on treated arm (P=0.005) were found as independent predictive factors of mean dose at multivariate analysis. A mean dose higher than 7 Gy and ROM abduction reduction more than 30° were related to DASH score level reduction. CONCLUSIONS: This hypothesis-generating study introduces an algorithm to be validated for management of sparing SHA and improving quality of survivorship. ROM evaluation after surgery, early physiotherapy, standard contouring, and planning adaptation represent possible indications to preserve shoulder impairment. Further prospective studies are needed to discriminate impairment of surgery and radiotherapy in order to personalized therapeutic plan programs.

EROS study: evaluation between high-dose-rate and low-dose-rate vaginal interventional radiotherapy (brachytherapy) in terms of overall survival and rate of stenosis.

PURPOSE: To compare the survival and toxicity outcomes in patients with endometrial cancer treated with either high-dose-rate (HDR) or low-dose-rate (LDR) vaginal brachytherapy (VBT) following external beam radiotherapy (EBRT). MATERIAL AND METHODS: From January 2000 to December 2014, patients with endometrial cancer after radical hysterectomy with/without pelvic and/or para-aortic lymphadenectomy were treated with adjuvant EBRT (45 Gy, 1.8 Gy/day to the whole pelvis) and subsequent VBT boost (HDR dose of 7 Gy in one fraction or LDR VBT dose of 25 Gy). The dose was prescribed at 0.5 cm from the surface of the applicator and the proximal half to two-thirds of the vagina was irradiated. The outcomes of patients were evaluated in terms of local control (LC), overall survival (OS), and rates of adverse events. RESULTS: We analyzed data of 200 patients treated with EBRT followed by HDR VBT boost in 78 patients and LDR VBT boost in 122 patients. With a median follow-up of 25 months (range, 6-163), 5-year OS was 98% and 97% in the LDR and HDR groups, respectively (p = 0.37). The 5-year LC was similar (93% in both groups) (p = 0.81). In multivariate analyses, none of the factors assessed (age, stage, grade) impacted OS (p = 0.37) or LC (p = 0.81). Patients treated with LDR VBT after EBRT had higher rates of acute gastrointestinal toxicity. No differences were found in acute genitourinary or hematological toxicities. Late toxicity such as vaginal stenosis was registered during regular follow-up visits and was similar in the two groups (p = 0.67). CONCLUSIONS: In our analysis, there were no differences in terms of OS and late toxicity outcomes for patients receiving LDR or HDR VBT. HDR VBT is a safe technique in comparison to LDR VBT.

INTERACTS (INTErventional Radiotherapy ACtive Teaching School) guidelines for quality assurance in choroidal melanoma interventional radiotherapy (brachytherapy) procedures.

Eye plaque brachytherapy represents a safe and effective therapeutic approach for choroidal melanoma, combining clinical outcomes with an eye and visual preservation. As it represents a complex procedure, a specific quality assurance program is strongly suggested to improve patients and operators safety, and to reduce possible complications linked to surgical procedure and radiation exposure. The aim of this paper is to describe the INTERACTS (Interventional Radiotherapy Active Teaching School) guidelines for quality assurance in choroidal melanoma interventional radiotherapy (brachytherapy) used in our institution.

Chemoradiation with concomitant boosts followed by radical surgery in locally advanced cervical cancer: long-term results of the ROMA-2 prospective phase 2 study.

PURPOSE: This prospective, phase 2 study aimed at assessing the efficacy of accelerated fractionation radiation therapy by concomitant boosts (CBs) associated with chemoradiation therapy (CRT) of the whole pelvis, in improving the rate of pathological complete response (pCR) to treatment in patients with International Federation of Gynaecology and Obstetrics (FIGO) stage IB2-IVA locally advanced cervical cancer. METHODS AND MATERIALS: Neoadjuvant CRT included conformal irradiation of the whole pelvis with a total dose of 39.6 Gy (1.8 cGy/fraction, 22 fractions), plus additional irradiation of primary tumor and parametria with 10.8 Gy administered with CBs (0.9 cGy/fraction, 12 fractions, every other day). Concomitant chemotherapy included cisplatin (20 mg/m(2), days 1-4 and 26-30 of treatment), and capecitabine (1300 mg/m(2)/daily, orally) during the first 2 and the last 2 weeks of treatment. Radical hysterectomy plus pelvic with or without aortic lymphadenectomy was performed within 6 to 8 weeks from CRT. Toxicity was recorded according to Radiation Therapy Oncology Group toxicity criteria and Chassagne grading system. Based on the Simon design, 103 cases were required, and the regimen would be considered active if >45 pCR were registered (α error = 0.05; ß error = 0.1). RESULTS: pCR was documented in 51 cases (50.5%), and the regimen was considered active, according to the planned statistical assumptions. At median follow-up of 36 months (range: 7-85 months), the 3-year local failure rate was 7%, whereas the 3-year disease-free and overall survival rates were 73.0% and 86.1%, respectively. Grade 3 leukopenia and neutropenia were reported in only 1 and 2 cases, respectively. Gastrointestinal toxicity was always grade 1 or 2. CONCLUSIONS: Addition of CBs in the accelerated fractionation modality to the whole pelvis chemoradiation followed by radical surgery results in a high rate of pathologically assessed complete response to CRT and a very encouraging local control rate, with acceptable toxicity.

Long-term analysis of gemcitabine-based chemoradiation after surgical resection for pancreatic adenocarcinoma.

PURPOSE: To evaluate the efficacy in terms of local control (LC) of 24 h infusion of gemcitabine plus radiotherapy after surgery for pancreatic cancer. METHODS: Weekly gemcitabine (100 mg/m(2)) was provided as a 24-hour infusion during the course of radiotherapy (50.4 Gy to the tumor, 39.6 Gy to the nodes). Patients subsequently received five cycles of gemcitabine monochemotherapy (1,000 mg/m(2) 1, 8, q21). The primary end point of the study was to achieve a 2-year LC rate of ≥80 % with type I and II errors of 5 and 20 %. The study was designed to accrue a maximum sample size of 35 patients. Secondary end points were toxicity evaluation, metastasis-free survival (MFS), and overall survival (OS). RESULTS: Data of 35 patients were available. Most of the patients (n = 27; 77.1 %) had duodeno-cephalo-pancreatectomy, 5 (14.3 %) distal pancreatectomy, and 3 (8.6 %) total pancreatectomy. The pathological stages were T1-T2 (n = 7; 20.0 %), T3-T4 (n = 28; 80.0 %), N0 (n = 17; 48.6 %), and N1 (n = 18; 51.4 %). Thirty patients (85.7 %) completed chemoradiation. Twenty-three patients (65.7 %) received further sequential chemotherapy. Acute toxicity was acceptable. No late toxicity occurred. The median follow-up period was 64 (range 24-118) months, and 2-year crude rate of LC was 83 (median not reached). Median MFS and OS were 26.5 and 22.5 months, respectively. CONCLUSIONS: The rate of LC met the main goal of the study. The regimen resulted in a high LC rate but failed to show a benefit in terms of OS or MFS, thus suggesting the need for a more intensified multimodal approach.

External beam radiotherapy plus 24-hour continuous infusion of gemcitabine in unresectable pancreatic carcinoma: long-term results of a phase II study.

PURPOSE: To evaluate the efficacy of gemcitabine-based chemoradiation (CT-RT) in treating patients (pts) affected by locally advanced pancreatic cancers (LAPC). METHODS AND MATERIALS: Weekly gemcitabine (100 mg/m(2)) was given as a 24-hour infusion during the course of three-dimensional radiotherapy (50.4 Gy to the tumor, 39.6 Gy to the nodes). After CT-RT, pts received five cycles of sequential chemotherapy with gemcitabine (1000 mg/m(2); 1, 8, q21). Response rate was assessed according to World Health Organization criteria 6 weeks after the end of CT-RT. Local control (LC), time to progression (TTP), metastases-free survival (MFS), and overall survival (OS) were analyzed by the Kaplan Meier method. RESULTS: Forty pts (male/female 22/18; median age 62 years, range, 36-76) were treated from 2000 to 2005. The majority had T4 tumour (n = 34, 85%), six pts (15%) had T3 tumour. Sixteen pts (40%) were node positive at diagnosis. Grade 3-4 acute toxicity was observed in 21 pts (52.5%). Thirty pts (75%) completed the treatment schedule. A clinical response was achieved in 12 pts (30%). With a median follow-up of 76 months (range, 32-98), 2-year LC was 39.6% (median, 12 months), 2-year TTP was 18.4% (median, 10 months), and 2-year MFS was 29.7% (median, 10 months). Two-year OS (25%; median, 15.5 months) compared with our previous study on 5-fluorouracil-based CT-RT (2.8%) was significantly improved (p <0.001). CONCLUSIONS: Gemcitabine CT-RT seems correlated with improved outcomes. Healthier patients who are likely to complete the treatment schedule may benefit most from this therapy.

Neoadjuvant chemoradiation followed by radical hysterectomy in FIGO Stage IIIB cervical cancer: feasibility, complications, and clinical outcome.

OBJECTIVE: To demonstrate the efficacy and feasibility of preoperative chemoradiation followed by radical surgery in a consecutive series of patients with stage IIIB cervical cancer. METHODS: Between October 1997 and July 2007, 39 patients with International Federation of Gynecology and Obstetrics stage IIIB cervical cancer were consecutively staged and treated at the Catholic University of Rome and Campobasso and at the National Cancer Institute of Milan. Radical surgery was performed 5 to 6 weeks after the end of the cisplatinum-based neoadjuvant chemoradiation. RESULTS: Clinical responses were observed in 35 patients (92.1%): 6 (15.8%) complete and 29 (76.3.8%) partial. Radical surgery was performed in 35 patients (89.7%). According to Chassagne classification, we observed 7 (20.0%) grade 3, 17 (48.6%) grade 2, and 28 (80%) grade 1 surgical complications. At pathological examination, 12 patients (34.3%) showed complete response, 7 patients (20.0%) had only a microscopic disease, 8 patients (22.8%) had a partial response, and the last 8 patients (22.8%) had no change in disease. We registered 11 (31.4%) operative and 4 (11.4%) early postoperative complications. Median follow-up was 33 months (range, 3-80 months). The percentages of 3-year disease-free survival and overall survival were 67.6% and 70.0%, respectively. Patients with complete response and microscopic disease showed better prognosis than patients with partial response and no change (3-year disease-free survival, 100% vs 31%; and 3-year overall survival, 100% vs 39%). CONCLUSIONS: Chemoradiation followed by radical hysterectomy could be administered in patients with stage IIIB cervical cancer with an acceptable rate of complications and with a survival outcome similar to that of chemoradiotherapy, allowing the assessment of pathological response with its implication on clinical outcomes.

Chemoradiation with concomitant boost followed by radical surgery in locally advanced cervical cancer: a dose-escalation study.

OBJECTIVE: Aim of this study is to evaluate the feasibility of an accelerated fractionation radiotherapy by concomitant boost in locally advanced cervical cancer patients, to explore the maximum tolerated dose (MTD) of radiation through a dose-escalation scheme, and to verify if increasing the radiation dose would result in a higher rate of pathologic complete response. METHODS: During the first and the last week of treatment, a combination of cisplatin (20 mg/mq/d, IV, days 1-4) and 5-fluorouracil (1 g/mq/d, continuous venous infusion, days 1-4) was administered. The dose escalation of external radiotherapy was delivered on the primary tumor, using the concomitant boost technique (CB, 90 cGy per fraction), delivering 3 different dose levels: (1) 1 weekly boost for a total dose of 4320 cGy; (2) 2 weekly boosts, total dose 4680 cGy; (3) 3 weekly boosts, total dose of 5040 cGy. RESULTS: Eighteen patients were submitted to a radiochemotherapeutic schedule of 3960 cGy in 22 fractions on pelvic lymph nodal stations. The MTD of radiation was not reached, being the only toxicities registered neutropenia G3 (n = 4), thrombocytopenia G3 (n = 1), stomatitis G3 (n = 1), diarrhea G3 (n = 2) easily managed. Six weeks after the end of radiochemotherapy, 17 patients were submitted to radical surgery, and are therefore evaluable for pathologic response. Among them, 15 complete remissions (88.2%, including 3 microscopical partial response), 1 partial response (5.9%), and 1 progression (5.9%) have been observed. CONCLUSIONS: These results demonstrate, even if in a small study, that this regimen of concurrent chemoradiation followed by radical surgery is well tolerated.

Squamous cell carcinoma antigen in follow-up of cervical cancer treated with radiotherapy: evaluation of cost-effectiveness.

PURPOSE: The squamous cell carcinoma (SCC) antigen is still considered the most accurate serologic tumor marker in cervical carcinoma. We assessed the contribution of the SCC assay to the detection of recurrences in patients treated with radiotherapy. METHODS AND MATERIALS: The pattern of recurrence and follow-up data were prospectively recorded for 135 patients. Of the 135 patients, 103 (76.3%) had primary cervical carcinoma and 32 (23.7%) had already experienced disease recurrence that had been successfully treated with surgery (n = 2), surgery plus radiotherapy (n = 2), radiotherapy (n = 5), or concomitant chemoradiotherapy (n = 23). The follow-up evaluations (chest X-ray, abdominopelvic magnetic resonance imaging, gynecologic examination with colposcopy, Papanicolaou smear, and SCC assay) were performed at 6-month intervals; the evaluation was done earlier if recurrent disease was suspected. The median follow-up time was 29 months (range, 6-131). The SCC serum levels were assayed, and a cost analysis was done. RESULTS: A total of 481 SCC determinations were performed. Of the 135 patients, 43 (31.8%) experienced disease recurrence. The SCC levels were higher in those with recurrent disease than in the disease-free patients. Elevation of SCC was documented in 34 (79.1% sensitivity) of 43 recurrences before symptoms appeared. Of the 38 patients with serum SCC elevation, 34 developed a recurrence (positive predictive value, 89.5%). Of the 97 patients with negative SCC serum levels, 88 had negative findings at the clinicoradiologic evaluation (negative predictive value, 90.7%). A simplified approach (SCC plus gynecologic examination) was evaluated. Compared with the complete follow-up program, the rate of missed recurrence was 2.2%. The total projected cost per patient for 5 years of follow-up for the simplified procedure was approximately 12.2-fold lower than the standard approach. CONCLUSIONS: Our results have shown that a simplified diagnostic approach, including the SCC assay and gynecologic examination, can detect a high rate of recurrence from cervical cancer, with a very favorable cost-effective profile.

Lymph node involvement in locally advanced cervical cancer patients administered preoperative chemoradiation versus chemotherapy.

BACKGROUND: A retrospective study was planned in 127 locally advanced cervical cancer (LACC) to investigate: (1) the rate and pattern of metastatic lymph node involvement in patients administered preoperative chemoradiation (CT/RT) versus neoadjuvant chemotherapy (NACT), and (2) the profile of clinico-pathological parameters predictive of metastatic lymph node involvement in these two clinical settings. Finally, we investigated whether the pathologically assessed status of lower pelvic nodes (LPN) was able to predict the pathologically assessed status of upper pelvic nodes (UPN) and parametrium in cases administered CT/RT. METHODS: Patients were selected including LACC patients who were administered concomitant CT/RT (n = 87) or NACT (n = 40), before radical surgery. RESULTS: Metastatic pelvic lymph node involvement was significantly lower in cases administered CT/RT (11.5%) compared to cases administered NACT (30.0%) (P value = 0.009). In the CT/RT group, only MRI-assessed pelvic node status (both at staging and post-treatment evaluation) was associated with pathologic pelvic node status. In patients administered CT/RT, the status of LPN appeared associated with the status of UPN. CONCLUSIONS: (1) Preoperative CT/RT treatment is associated with a lower rate of pelvic node disease in LACC patients compared to NACT; (2) there is no association between the preoperative extent of residual cervical disease after CT/RT and pathologically assessed pelvic node status; (3) the pathological status of LPN is predictive of the pathological status of UPN and parametrium.

Anemia in patients with locally advanced cervical carcinoma administered preoperative radiochemotherapy: association with pathological response to treatment and clinical outcome.

OBJECTIVE: The aim of this study was to investigate the role of anemia at presentation (basal HB) and during treatment (nadir HB) as predictor of pathological response, as well as disease-free (DFS) and overall survival (OS) in LACC patients undergoing chemoradiation followed by radical surgery. METHODS: 114 consecutive LACC patients were accrued at the Gynecologic Oncology Unit, Catholic University, Rome and at the Department of Oncology, Catholic University of Campobasso, Italy. Neoadjuvant treatment included chemotherapy with cisplatin (20 mg/m2) and 5-fluorouracil (1000 mg/m2, 24-h infusion) (both on days 1-4 and 27-30) and external radiotherapy to the whole pelvic region (22 fractions, 1.8 Gy/day, totaling 39.6 Gy). Clinical responders underwent radical surgery. Hemoglobin levels were recorded and expressed in gram per literx10(-2) (g/dl). The value of 10 g/dl was arbitrarily chosen as cut-off value. RESULTS: In cases showing high basal HB status, the percentage of pathological response was significantly higher than in patients showing low HB status (76.3% versus 46.7%) (P value=0.027). When logistic regression was applied, only advanced stage remained associated with a poor chance of response to treatment. Cases with low basal HB status had a shorter DFS and OS than cases with a high HB status (P value=0.0001 and 0.0022, respectively). Similar results were obtained when analyzing nadir HB status. In multivariate analysis, high basal HB status, and advanced stage, retained an independent negative prognostic role for DFS and OS. CONCLUSIONS: Anemia identifies LACC patients administered preoperative radiochemotherapy, who are at higher risk of recurrence and death of disease.

Chemoradiation and brachytherapy in biliary tract carcinoma: long-term results.

PURPOSE: To evaluate long-term effects of chemoradiation and intraluminal brachytherapy in terms of local control, disease-free survival, overall survival, and symptom relief in patients with unresectable or residual extrahepatic biliary carcinoma. METHODS AND MATERIALS: Twenty-two patients with unresectable (17 patients) or residual (5 patients) nonmetastatic extrahepatic bile tumors received external beam radiation therapy (39.6-50.4 Gy) between 1991 and 1997. In 21 patients, 5-fluorouracil (96-h continuous infusion, Days 1-4, 1,000 mg/m2/day) was administered. Twelve patients received a boost of intraluminal brachytherapy with 192Ir wires (30-50 Gy) 1 cm from the source axis. RESULTS: During external beam radiotherapy, 10 patients (45.4%) developed Grade 1 to 2 gastrointestinal toxicity. In patients with unresectable tumor who could be evaluated, the clinical response was 28.6% (4 of 14). Two patients showed complete response. In all 22 patients, median durations of local control, disease-free survival, and overall survival were 44.5 months, 16.3 months, and 23.0 months, respectively. Two patients who received external beam radiation therapy and intraluminal brachytherapy developed late duodenal ulceration. In patients with unresectable tumors, median survival was 13.0 months and 22.0 months in those treated with and without brachytherapy, with 16.7% and no 5-year survival, respectively (p=0.607). Overall 5-year survival was 18.0%: 40% and 11.7% in patients treated with partial resection and in those with unresectable tumor, respectively (p=0.135). CONCLUSION: This study confirmed the role of concurrent chemoradiation in advanced biliary carcinoma; the role of intraluminal brachytherapy boost remains to be further analyzed in larger clinical trials.

Concurrent 5-fluorouracil, mitomycin C and radiation with or without brachytherapy in recurrent cervical cancer: a scoring system to predict clinical response and outcome.

AIMS AND PURPOSE: This is a prospective, phase II study aimed to evaluate the effect of concurrent 5-fluorouracil, mitomycin C, and radiation with or without brachytherapy on the clinical outcome of a series of recurrent cervical cancer patients and to determine the prognostic impact of a subset of factors. METHODS: Thirty-three patients with locally recurrent, non-metastatic cervical cancer received external beam radiation (4-week split course: 23.4 + 23.4 Gy) plus two courses of concomitant chemotherapy (5-fluorouracil, 96-h continuous infusion, days 1-4, 1 g/m2/day; mitomycin C, 10 mg/m2, bolus i.v., day 1). Twelve patients with vaginal recurrence (36.4%) underwent endocavitary low-dose rate brachytherapy boost (20-25 Gy); 11 patients with lateral pelvic recurrence (33.3%) received external beam radiation boost (14-20 Gy). RESULTS: Fourteen complete responses (42.4%), 7 partial responses (21.2%), 5 disease stabilizations (15.1%) and 7 progressions (21.2%) were obtained. After a median follow-up of 34 months (range, 6-127), overall actuarial 3-year survival, progression-free survival and local progression-free survival were 59.7%, 48.1% and 51.7%, respectively. Patients with vaginal recurrence of less than 4 cm and negative lymph nodes proved to respond best to the treatment. Two patients (6.1%) experienced hematologic grade 3 toxicity. One patient had grade 3 intestinal toxicity (3.0%). No patient had major skin or urological acute toxicity. Severe late toxicity was infrequent. Three patients had prolonged leukopenia (9.0%). Four patients showed severe vaginal stenosis (12.1%). A clinical score of 0 to 1 was assigned to each patient on the basis of the absence (score = 0) or presence (score = 1) of any of the following prognostic factors: time between surgery and recurrence shorter than 12 months, pelvic wall site of recurrence, positive lymph nodes, hemoglobin < 11 g/dL. Using this system, it was clear that patients with a low total score had a significantly better outcome (clinical remission, 51% of patients with a score < or = 2 vs 12% of patients with a score > 2, P = 0.06), local control of the disease (65% vs 20% after 3 years, P = 0.001,) and overall survival (75% vs 30% after 3 years, P = 0.032). CONCLUSIONS: Our data suggest that this combined modality therapy was relatively well tolerated and resulted in reasonable local control and survival. The scoring system proved to be helpful to identify patients with the greatest chance of benefiting from the treatment. Further studies are probably needed to salvage the other patients, whose prognosis remains severe.

Radiation-induced cardiovascular disease: impact of dose and volume.

The radiation-induced cardiovascular pathology represents a major cause of morbidity and mortality in patients undergoing therapeutic chest irradiation. There is a broad range of clinical manifestations probably associated with dose, volume and technique of irradiation. From the assumption that prevention is the best way to manage radiation-induced cardiotoxicity, based on the pathophysiogenesis of heart structures, a number of reports of the literature are reviewed. They consider the incidence of cardiovascular disease in patients affected by Hodgkin's lymphoma and breast cancer. The dosimetric prevention is takled in terms of therapeutic procedures and doses (IMRT, 3DCRT) with particular reference to the impact on cardiotoxicity of parameters as maximum heart distance (MHD), mean lung dose (MLD), normal tissue complication probability (NTCP) and V30. The different evaluation criteria of cardiotoxicity are reported, based on the review of the major scoring scales of acute and late complications, which have been worked out in the course of time (LENT-SOMA, RTOG, CTC v.2.0 and CTC v.3.0). The monitoring system of late toxicity used by the authors is presented.

Radiotherapy-related fatigue: incidence and predictive factors.

Radiotherapy-induced fatigue is a common early and chronic side-effect of irradiation, reported in up to 80% and 30% of patients respectively during radiation therapy and at follow-up visits. The factors that cause fatigue and the exact mechanisms responsible for its production, sustenance, or amelioration are not well understood. Multiple correlates and mechanisms have been proposed in the literature and integrated within models of cancer-related fatigue. A multidimensional approach in clinical practice is proposed based on the evaluation of cancer-related fatigue, and on the development of an adequate management. The monitoring system of fatigue used by the authors is presented.