The Benefit of Zinc Sulfate in Oropharyngeal Mucositis during Hyperfractionated Accelerated Concomitant Boost Radiotherapy with Concurrent Cisplatin for Advanced-Stage Oropharyngeal and Hypopharyngeal Cancers.

BACKGROUND: Radiation-induced oropharyngeal mucositis is a major problem causing widespread clinical symptoms and may interfere with treatment plans, ultimately jeopardizing patient outcome. Zinc supplementation may be considered beneficial in preventing acute toxicity during chemoradiation. AIMS AND OBJECTIVE: The aim of the study is to determine the effect of zinc supplementation on radiation-induced oropharyngeal mucositis in Stage III and IV-A oropharynx and hypopharynx cancers treated by hyperfractionated accelerated concomitant boost radiotherapy with weakly cisplatin. The objective behind the study is to know any changes in the onset, duration, and severity of oropharyngeal mucositis by implementation of oral zinc sulfate. MATERIALS AND METHODS: The study is double-blinded randomized controlled assessment involving 120 patients (60 - control and 60 - experimental) treated with chemoradiation for oropharyngeal and hypopharyngeal cancers. The experimental group received oral zinc sulfate 150 mg once daily during and after treatment, whereas the control group patients were given placebo. The categorical data were analyzed using the Chi-square test and Pearson correlation. The Friedman test was used for comparison of oral mucositis grading between the groups. RESULTS: A statistically significant difference was found in the zinc-supported experimental group showing delay in onset, decrease in severity, and duration of oropharyngeal mucositis. CONCLUSION: Zinc supplementation could be beneficial in managing oropharyngeal mucositis during chemoradiation of head-and-neck cancers with no untoward side effects.

Hypofractionation with concomitant boost using intensity-modulated radiation therapy in early-stage breast cancer in Mexico.

AIM: To evaluate whether hypofractionation with integrated boost to the tumour bed using intensity-modulated radiation therapy is an acceptable option and to determine whether this treatment compromises local control, toxicity and cosmesis. BACKGROUND: Retrospective studies have demonstrated that patients who are treated with HF and integrated boost experience adequate local control, a dosimetric benefit, decreased toxicity and acceptable cosmesis compared with conventional fractionation. MATERIALS AND METHODS: A retrospective, observational and longitudinal study was conducted from January 2008 to June 2015 and included 34 patients with breast cancer (stage 0-II) who were undergoing conservative surgery.The prescribed doses were 45 Gy in 20 fractions (2.25 Gy/fraction) to the breast and 56 Gy in 20 fractions (2.8 Gy/fraction) to the tumour bed. RESULTS: Thirty-four patients were included. The mean follow-up was 49.29 months, and the mean age was 52 years. The mean percentage of PTV from the mammary region that received 100% of the prescribed dose was 97.89% (range 95-100), and the mean PTV percentage of the tumour bed that received 100% of the dose was 98% (95-100).The local control and the overall survival were 100%, and the cosmesis was good in 82% of the patients. Grade 1 acute toxicity was present in 16 patients (47%), and grade 1 chronic toxicity occurred in 6 cases (18%). CONCLUSION: The results of the present study demonstrate that hypofractionation with integrated boost using intensity-modulated radiation therapy is an acceptable option that provides excellent local control and low toxicity.

Muscle-invasive bladder cancer treated with TURB followed by concomitant boost with small reduction of radiotherapy field with or without of chemotherapy.

AIM: To evaluate the clinical outcome and toxicity of the treatment of muscle-invasive bladder cancer (MIBC) that combined transurethral resection of bladder tumor (TURB) with "concomitant boost" radiotherapy delivered over a shortened overall treatment time of 5 weeks, with or without concurrent chemotherapy. BACKGROUND: Local control of MIBC by bladder-sparing approach is unsatisfactory. In order to improve the effectiveness of radiotherapy, we have designed a protocol that combines TURB with a non-conventionally fractionated radiotherapy "concomitant boost". MATERIALS AND METHODS: Between 2004 and 2010, 73 patients with MIBC cT2-4aN0M0, were treated with "concomitant boost" radiotherapy. The whole bladder with a 2-3 cm margin was irradiated with fractions of 1.8 Gy to a dose of 45 Gy, with a "concomitant boost" to the bladder with 1-1.5 cm margin, during the last two weeks of treatment, as a second fraction of 1.5 Gy, to a total dose of 60 Gy. Radiochemotherapy using mostly cisplatin was delivered in 42/73(58%) patients, 31/73(42%) patients received radiotherapy alone. RESULTS: Acute genitourinary toxicity of G3 was scored in 3/73(4%) patients. Late gastrointestinal toxicity higher than G2 and genitourinary higher than G3 were not reported. Complete remission was achieved in 48/73(66%), partial remission in 17/73(23%), and stabilization disease in 8/73(11%) patients. Three- and five-year overall, disease specific and invasive locoregional disease-free survival rates were 65% and 52%, 70% and 59%, 52% and 43%, respectively. CONCLUSIONS: An organ-sparing approach using TURB followed by radio(chemo)therapy with "concomitant boost" in patients with MIBC allows to obtain long-term survival with acceptable toxicity.

Concomitant Boost With Six Fractions of Radiation a Week in Locally Advanced Head and Neck Cancer Patients: A Prospective Study.

Background and objective Radiation therapy plays a significant role in the radical treatment of locally advanced head and neck cancers. Studies have shown the radiobiological advantage of accelerated chemoradiation over conventional chemoradiation as it reduces the chances of accelerated repopulation and decreases overall treatment time. This study aimed to assess the response and toxicities of accelerated concomitant chemoradiation in locally advanced head and neck cancer patients. Methods A total of 51 patients were enrolled and treated with accelerated concomitant chemoradiation, receiving one fraction of radiation per day, six fractions per week, with the sixth fraction as a boost on Saturdays, with weekly concurrent cisplatin at 40 mg/m2. Patients were followed up till six months after treatment completion. Radiological investigation was done to assess response according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.128, and acute toxicities were assessed according to Radiation Therapy Oncology Group (RTOG) criteria. Results The median follow-up period was six months; 28 patients (62.22%) had a complete response and 17 (37.78%) had a partial response at six months post-completion of the treatment. The maximum acute toxicities developed at the completion of treatment. Grade III and IV mucositis developed in 14 patients (31.11%) and grade III dermatitis developed in one patient (2.22%), without any grade IV dermatitis during the total duration of treatment. The toxicities were manageable, and most of them resolved after three months of treatment completion. Conclusions Accelerated concomitant chemoradiation with six fractions of radiation in a week led to a decrease in overall treatment time. Of note, 62.22% of patients had complete remission, with manageable acute mucositis and dermatitis, which resolved in 82% and 67%, respectively within three months of treatment completion. However, further studies involving larger samples and longer follow-ups are needed for this regimen to be established as the standard of care in the future.

Trimodality Therapy in which Concurrent Chemoradiation with Concomitant Boost in Muscle Invasive TCC Urinary Bladder Cancer.

BACKGROUND: Bladder cancer is the most common genitourinary tract malignancy among Egyptian males (16%). bladder sparing therapy can be considered an alternative for patients refusing surgery or are not candidates for surgery. The objective of this study was to determine the safety and feasibility of external-beam irradiation with concomitant boost in muscle invasive bladder cancer and to determine the short-term (1-year) risk of recurrence of bladder cancer. METHODS: Between October 2019 and November 2021, we enrolled 42 patients in Prospective, one arm trial. Eligible patients had pathologically confirmed TCC transitional cell carcinoma of the bladder cT2-4aN0M0, who refused surgery or had contraindications to surgery, and treated conservatively with radiotherapy. All patients underwent maximal TURB before beginning of chemoradiation therapy which was delivered in all patients The patients received radiotherapy dose 45 Gy/25 fractions (1.8 Gy) per fraction to the whole bladder+ 3 cm. with   concurrent cisplatin 20 mg/ m2 over 30 minutes  before radiation on days 1,2,15,16,29, and 30. Additionally, concomitant boost limited to the bladder plus1.5 cm margin was deliverd during the last ten days of the treatment with a minimum 6 h gap between fractions, to a total dose 60 Gy, with the overall treatment time equal to 5 weeks. RESULTS: The median overall survival OS for 42 patients with transitional cell carcinoma( TCC) of bladder treated with 3D conformal radiotherapy 3DCRT and concomitant boost was 28 months, the mean OS was 29.9±1.04, and (95% confidence interval=27.9-32). The one-year OS was 100%, 2-year OS was 81%, and 3-year OS was 26.2%.The mean loco-regional relapse free survival (LRRFS) was 31.6±1.8, 95% CI=28.1-35.1, and the median was 26.5±1.4, the one-year loco-regional RFS was 92.9%, and 2-year (LRRFS) was 66.7%.Acute and late genitourinary toxicity was grade 2 in most of patients and also acute and late toxicity of gastrointestinal was equal or less than grade 1. CONCLUSION: In external radiotherapy for muscle invasive bladder cancer a concomitant boost technique of invasive bladder cancer with shortening of the overall treatment time provides a high probability of local control and overall survival with acceptable toxicity.

A Comparison of the Toxicities in Patients With Locally Advanced Head and Neck Cancers Treated With Concomitant Boost Radiotherapy Versus Conventional Chemoradiation.

PURPOSE: To compare the objective and patient-reported toxicities of concomitant boost radiotherapy (CBRT) and concurrent chemoradiation (CRT) in patients with locally advanced head and neck cancers. METHODS AND MATERIAL: In this prospective study, 46 patients with histologically proven stage III-IVA head and neck cancer were randomly assigned to receive either concurrent chemoradiation to a dose of 66 Gy in 33 fractions over 6.5 weeks with concurrent cisplatin (40 mg/m2 IV weekly; control arm) or accelerated radiotherapy with concomitant boost radiotherapy (study arm) to a dose of 67.5 Gy in 40 fractions in five weeks. Acute toxicity was evaluated using RTOG toxicity criteria. The assessment was done weekly after initiation of treatment, at the first follow-up (six weeks), and at three months. The four main patient-reported symptoms of pain, hoarseness of voice, dryness of mouth, and loss of taste were also compared between the two groups to assess patient quality of life during treatment. RESULTS: The mean treatment duration was 37 days in the CBRT arm and 49 days in the CRT arm. Treatment-related interruptions were less in the study group,17.3% in the study, and 27.2% in the control with insignificant P-value. Grade III laryngeal toxicity was significantly higher in the study group (P=0.029). Other acute grade I-III toxicities (pharyngeal, skin, mucositis, and salivary) were comparable in both CRT and CBRT arms. Grade IV toxicities were seen only in the CBRT arm but were resolved at the first follow-up. Haematological toxicities and renal toxicities were significantly higher in the CRT arm, with significant P-values of 0.0004 and 0.018, respectively. CONCLUSION: In patients with locally advanced head and neck cancer, concomitant boost radiotherapy is well tolerated with acceptable local toxicity and minimal systemic toxicity as compared to conventional chemoradiation. It is a feasible option for patients with locally advanced head and neck cancer not fit for concurrent chemoradiation.

Elective pelvic nodal irradiation with a simultaneous hypofractionated integrated prostate boost for localized high risk prostate cancer: Long term results from a prospective clinical trial.

BACKGROUND: To report on long-term results of elective pelvic nodal irradiation (EPNI) and a simultaneous hypofractionated prostate boost for high-risk prostate cancer. MATERIALS AND METHODS: This was a prospective single-arm study. Patients with high-risk disease (cT3, PSA >20 ng/mL, or Gleason score 8-10) were eligible. Patients received 45 Gy in 25 fractions to the prostate and pelvic lymph nodes with a simultaneous intensity-modulated radiotherapy boost of 22.5 Gy to the prostate (total dose 67.5 Gy in 25 fractions), with androgen deprivation therapy (ADT) for 2-3 years. The primary endpoint was biochemical failure. Secondary endpoints included distant metastases and overall survival. Multivariable analysis was performed to look for predictive factors. Late toxicity was assessed using CTCAE v3.0. RESULTS: 230 patients enrolled. Median follow-up was 11.2 years (IQR 8.1-12.9). At 10 years, cumulative incidence of biochemical failure was 33.4%, distant metastasis was 16.5%, and overall survival was 76.3%. On multivariable analysis, PSA nadir ≥0.05 ng/mL was associated with biochemical failure (HR 6.8, 95% CI 4-11.8, p < 0.001) and distant metastases (HR 7.5, 95% CI 3.9-14.5, p < 0.0001). PSA nadir ≥0.1 ng/mL (HR 5.2, 95% 2.2-12, p = 0.0001) and ADT use ≤12 months (versus >24 months) (HR 2.3, 95% CI 1.3-3.9, p = 0.004) were associated with worse survival. The 5-year cumulative incidence of any late grade ≥3 gastrointestinal and genitourinary toxicity was 2.3% and 7.5%, respectively. CONCLUSION: EPNI and a simultaneous hypofractionated prostate boost combined with long-term ADT for high-risk prostate cancer resulted in acceptable 10-year biochemical control and survival with low grade ≥3 toxicity.

Accelerated Fractionation With Concomitant Boost vs. Conventional Radio-chemotherapy for Definitive Treatment of Locally Advanced Squamous Cell Carcinoma of the Head-and-Neck (SCCHN).

BACKGROUND/AIM: Patients with unresectable head-and-neck cancer (SCCHN) unable to tolerate radiochemotherapy may receive unconventionally fractionated radiotherapy. This retrospective study compared both treatments. PATIENTS AND METHODS: Eight patients unsuitable for chemotherapy were assigned to accelerated fractionation with concomitant boost (AF-CB, 69.6 Gy/39 fractions) over 5.5 weeks (group A) and 72 patients to cisplatin-based radiochemotherapy (70 Gy/35 fractions) over 7 weeks (group B). Groups were matched (cancer site, gender, age, performance score, T-/N-stage, histologic grade) and compared for loco-regional control (LRC), metastases-free survival (MFS), overall survival (OS) and toxicities. RESULTS: LRC, MFS, OS and radiation-related toxicities were not significantly different between groups A and B. Improved outcomes were associated with favorable cancer site, better performance score and T3-stage. In group B, toxicity led to reduction/discontinuation of chemotherapy in 38.9% and interruptions of radiotherapy >7 days in 19.3% of patients. CONCLUSION: AF-CB appeared a reasonable alternative for patients who cannot safely receive radio-chemotherapy for unresectable SCCHN.

Comparison of Conventional Fractionation and Accelerated Fractionation With Concomitant Boost for Radiotherapy of Non-metastatic Stage IV Head-and-Neck Cancer.

BACKGROUND/AIM: Some patients with unresectable or incompletely resected head-and-neck cancer (SCCHN) cannot tolerate radiochemotherapy. Alternatives are needed that are more effective than conventional radiotherapy alone. PATIENTS AND METHODS: This retrospective study investigated patients irradiated for non-metastatic stage IV SCCHN who could not receive concurrent chemotherapy. Eight patients received accelerated radiotherapy with concomitant boost (group A) and 31 patients conventionally fractionated radiotherapy (group B). Groups were matched for tumor site, gender, age, performance score and histologic grade. RESULTS: Two-year PFS-rates were 63% in group A vs. 41% in group B, and median PFS-times were 36 vs. 10 months (p=0.48). Two-year OS-rates were 88% vs. 37%, and median OS-times were 44 vs. 14 months (p=0.19). Grade ≥2 radiation dermatitis was significantly (p=0.040) more common in group B; other toxicities were similar. CONCLUSION: Accelerated fractionation with concomitant boost appeared superior to conventional fractionation and can be considered for patients with stage IV SCCHN not suitable for radiochemotherapy. Larger studies are needed to confirm these findings.

Elective Pelvic Nodal Irradiation With a Simultaneous Hypofractionated Integrated Prostate Boost for Localised Prostate Cancer: Ready for Prime Time?

External beam radiotherapy is a standard treatment option for localised prostate cancer and hypofractionation has become an alternative to conventionally fractionated radiotherapy. In patients who receive external beam radiotherapy, elective pelvic nodal irradiation is sometimes delivered, especially in patients with unfavourable disease who are at risk of micrometastatic spread of cancer into the regional nodes. One elegant approach to combine prostate hypofractionation with elective pelvic nodal irradiation is with a simultaneous integrated boost technique, where a radical hypofractionated dose is delivered to the prostate while the regional pelvic nodes receive a lower microscopic dose simultaneously in a single radiotherapy plan over the same number of treatment fractions. This article reviews the existing published literature evaluating such an approach.

Intensity-Modulated Radiotherapy with Concomitant Boost After Breast Conserving Surgery: A Phase I-II Trial.

PURPOSE: A concomitant boost (CB) in patients treated with postoperative radiotherapy after conservative surgery of invasive breast cancer (BC) has been suggested for treatment time reduction and therapy intensification. The aim of this analysis was to assess long-term tolerability of a CB in patients treated with postoperative intensity Modulated Accelerated RAdiotherapy (MARA). PATIENTS AND METHODS: In this phase I-II trial, 321 patients with intermediate-high risk BC (pT1-4 with at least one of the following characteristics: pre or perimenopausal status, pN2-3, positive or close margins) were enrolled. Patients were treated with forward-planned intensity modulated radiotherapy (IMRT) and CB. A total dose of 50 Gy (2 Gy/fraction) and 60 Gy (2.4 Gy/fraction) was prescribed to the whole breast and the tumor bed, respectively. The potential impact of hypertension, diabetes, smoking habit, alcohol consumption, chemotherapy, and hormone therapy on both skin and subcutaneous late toxicity-free survival (LTFS) was evaluated. Survival curves were calculated using the Kaplan-Meier method. RESULTS: Median follow-up was 52 months (range: 3-115). Regional node irradiation, adjuvant chemotherapy and hormonal therapy were prescribed to 29.3%, 65.4% and 81.0% of patients, respectively. Five-year G2 and G3 skin LTFS were 95.6% and 100.0%, respectively. Five-year G2 and G3 subcutaneous LTFS were 80.0% and 98.6%, respectively. Only diabetes showed a significant correlation with worse G3 subcutaneous LTFS (p: 0.024). Five-year loco-regional control, metastasis-free survival, disease-free survival, and overall survival were 98.0%, 91.8%, 89.7% and 96.3%, respectively. CONCLUSION: IMRT combined with CB was associated with a low risk of > G2 late toxicities (0.0% and 1.4% for skin and subcutaneous tissue, respectively). The cumulative actuarial incidence of local recurrences was 2.0% despite the exclusion of low-risk patients. Our results suggest that CB is safe and effective in patients with intermediate-high risk BC. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03471741.

A comparative study of concomitant boost radiation versus concomitant boost with concurrent chemoradiation versus standard fractionation chemoradiation in locally advanced head-and-neck cancer.

CONTEXT: As the number of head-and-neck cancer (HNC) patients are high in our subcontinent, the study was designed to reduce the treatment time and increase efficacy. AIMS: Comparative evaluation of the efficacy, toxicity, local control, and survival of concomitant boost radiotherapy (CBRT), CBRT with concurrent chemoradiation (CBRT + CCT) and conventionally fractionated radiotherapy with concomitant chemotherapy (CFRT + CCT) in locally advanced HNC (LAHNC). MATERIALS AND METHODS: Patients with LAHNC were randomly assigned to 3-groups of 30-patients each. Group I (CBRT) received, 45 Gy/25#/5-weeks and 18 Gy/10# concomitant boost in the last 2-week of treatment, receiving a total dose of 63 Gy. Group II (CBRT + CCT) received CBRT with concomitant cisplatin 75 mg/m 2 on day 1, 17, and 34. Group III (CFRT + CCT) received 64 Gy/32#/6.2 weeks, concurrent with injection cisplatin 75 mg/m 2 on day 1, 22, and 42. STATISTICAL ANALYSIS USED: Stata 9.0 SPSS and Chi-square test were used for analysis and disease-free survival (DFS) rates were calculated using the Kaplan-Meier method. RESULTS: The median follow-up period was 8.2 months. At last follow-up, locoregional control was 36%, 57%, and 40% and DFS was seen in 33%, 53%, and 40% of patients in Group I, II, and III, respectively. Grade-3 cutaneous reactions were significantly higher in Group-II as compared to that of Group-III (P = 0.033) and Group-I (P = 0.715). CONCLUSION: All three groups have similar response rates and DFS with manageable toxicity.

The Promising Treatment Schedule of Concurrent Chemoradiotherapy for Stage III Non-small Cell Lung Cancer: Alternative for Conventional Fractionation Using Mathematical Analysis.

BACKGROUND/AIM: To evaluate treatment schedules involving concurrent chemoradiotherapy in stage III non-small cell lung cancer (NSCLC) using the tumor control probability (TCP) and normal tissue complication probability (NTCP) parameters. PATIENTS AND METHODS: The standard schedules were compared with two types of schedules, the dose escalation and the short-term schedules. Standard schedules were 60-74 Gy in 30-37 fractions. The dose escalation schedules with hypofractionation and hyperfractionation were 69 Gy in 30 fractions and 69.6 Gy in 58 fractions, respectively, twice per day (b.i.d). The short-term schedules were concomitant boost, 64 Gy in 40 fractions b.i.d. and the accelerated radiotherapy schedule, 57.6 Gy in 36 fractions, three fractions per day (t.i.d). RESULTS: The average TCP for the short-term schedules was more than 16% in two tumor models; however, the TCP for standard and dose escalation schedules was less than 5%. In each organ, the increase in NTCP for the short-term schedule compared with standard schedules was less than 15%. CONCLUSION: The short-term schedules had an advantage over standard schedules for NSCLC.

Predictors of Acute Radiation Esophagitis in Non-small Cell Lung Cancer Patients Treated With Accelerated Hyperfractionated Chemoradiotherapy.

BACKGROUND/AIM: To identify the clinical and dosimetric predictors of severe acute radiation esophagitis (RE) in patients with non-small cell lung cancer (NSCLC) treated with accelerated hyperfractionated concurrent chemoradiotherapy (AH-CCRT) with concomitant boost technique. PATIENTS AND METHODS: A total of 159 patients who underwent AH-CCRT (64 Gy in 40 fractions twice daily) were retrospectively identified. Severe RE was designated as grade 3 or higher according to the Common Terminology Criteria for Adverse Events, version 4.0. RESULTS: The incidence rate of grade 3 RE was 15.1% (24/159). The multivariate analysis that incorporated the Eastern Cooperative Oncology Group performance status (ECOG PS, ≥1 vs. 0) and the relative esophagus volume irradiated with at least 60 Gy (V60) was optimal. Patients with a V60 of ≥15% had a 37.8% risk of grade 3 RE compared to a 6.1% risk among those with a V60 of <15%. CONCLUSION: ECOG PS (≥1 vs. 0) and the V60 were found to be significant risk factors for severe RE in NSCLC patients who underwent AH-CCRT.

Simulation study of dosimetric effect in proton beam therapy using concomitant boost technique for unresectable pancreatic cancers.

PURPOSE: The purpose of this study is to investigate the dose distribution of proton beam therapy (PBT) using a concomitant boost technique for unresectable pancreatic cancers. MATERIALS AND METHODS: This simulation study involved 36 patients with unresectable pancreatic cancer. The irradiation dose was set as 67.5 gray equivalent (GyE) with 25 fractions using concomitant boost technique. The irradiation dose was set as 50 GyE to cover the whole target and another posterior beam of 17.5 GyE was added to ensure that 10% isodose line was not delivered to the gastrointestinal (GI) tract. Dose distribution of the gross tumor volume and GI tract was examined. RESULTS: V55GyE, 60GyE, 65GyE were 80.8, 66.5, and 42.4%, respectively, and mean dose was 64.1 GyE in all patients. The distance from the GI tract showed significant difference in dose distribution (P = 0.002 in V55GyE, 0.0009 in V60GyE, 0.003 in V65GyE, and 0.02 in mean dose, respectively). Location, tumor diameter, or lymph nodes metastasis did not show any difference. CONCLUSIONS: We found that irradiated dose is closely related to the distance from the GI tract. Clinically, this protocol is expected to have outstanding effects on local control of tumors compared to conventional PBT.

The Role of Concomitant Radiation Boost in Neoadjuvant Chemoradiotherapy for Locally Advanced Rectal Cancer.

BACKGROUND/AIM: This study analyzed the impact of concomitant boost on long-term clinical outcomes in locally advanced rectal cancer. PATIENTS AND METHODS: A total of 141 patients (median age=61 years) were treated with neoadjuvant chemoradiotherapy. Median total dose was 50.4 Gy. Forty-three patients received a concomitant boost. Concurrent chemotherapy consisted of 5-fluorouracil (5-FU), given as a 24-h continuous infusion. Mean follow-up was 83.7 months. RESULTS: The 3, 5-, and 10-year overall survival (OS) rates were 91.9%, 84.6%, and 52.9%, respectively. Recurrence-free survival (RFS) rates at 3, 5, and 10 years were 91.4%, 88.9%, and 79.3%, respectively. Metastasis-free survival (MFS) rates at 3, 5, and 10 years were 84.6%, 75.4%, and 49.9%, respectively. Overall, 9.9% of all patients achieved pathological complete response. Down-staging of T- or N-stage was achieved in 55.1% and 41.5% of patients. Multivariate analysis revealed that female sex (p=0.011), concomitant boost-radiotherapy (p=0.014), and the presence of fewer than five positive lymph nodes (p<0.001) were positive predictors of OS. Fewer than five positive lymph nodes was also a positive predictor for RFS (p=0.019). Female gender (p=0.018) and fewer than five positive lymph nodes (p<0.001) were significant predictors for MFS. CONCLUSION: Our data support the efficacy of preoperative treatment for rectal cancer in terms of local outcomes. Intensified radiotherapy using a concomitant boost has a positive effect on OS.

Ten-year results of accelerated hypofractionated adjuvant whole-breast radiation with concomitant boost to the lumpectomy cavity after conserving surgery for early breast cancer.

Accelerated hypofractionated whole-breast radiotherapy (WBRT) is considered a standard therapeutic option for early breast cancer (EBC) in the postoperative setting after breast conservation (BCS). A boost to the lumpectomy cavity may further increase local control. We herein report on the 10-year results of a series of EBC patients treated after BCS with hypofractionated WBRT with a concomitant photon boost to the surgical bed over 4 weeks. Between 2005 and 2007, 178 EBC patients were treated with a basic course of radiotherapy consisting of 45 Gy to the whole breast in 20 fractions (2.25 Gy daily) with an additional boost dose of 0.25 Gy delivered concomitantly to the lumpectomy cavity, for an additional dose of 5 Gy. Median follow-up period was 117 months. At 10-year, overall, cancer-specific, disease-free survival and local control were 92.2% (95% CI 88.7-93.4%), 99.2% (95% CI 96.7-99.7%), 95.5% (95% CI 91.2-97.2%) and 97.3% (95% CI 94.5-98.9%), respectively. Only eight patients recurred. Four in-breast recurrences, two axillary node relapses and two metastatic localizations were observed. Fourteen patients died during the observation period due to other causes while breast cancer-related deaths were eight. At last follow-up, ≥G2 fibrosis and telangiectasia were seen in 7% and 5% of patients. No major lung and heart toxicities were observed. Cosmetic results were excellent/good in 87.8% of patients and fair/poor in 12.2%. Hypofractionated WBRT with concomitant boost to the lumpectomy cavity after BCS in EBC led to consistent clinical results at 10 years. Hence, it can be considered a valid treatment option in this setting.

An accelerated hypofractionated schedule with a daily concomitant boost after breast conservation surgery: the feasibility and toxicity.

AIMS AND BACKGROUND: Reduction of overall treatment time of postoperative irradiation and evaluation of the feasibility and preliminary toxicity of an accelerated hypofractionated whole breast irradiation with an addition of a concomitant daily boost in patients with early breast cancer submitted to conservation surgery. MATERIALS: Between June 2010 and September 2011, 122 patients underwent accelerated hypofractionated adjuvant radiation after conservation surgery (pT1 or pT2, pN0-N1). Radiotherapy consisted of 45 Gy, to the whole breast in 20 fractions with 2.25 Gy/fraction; an additional daily boost dose of 0.25 Gy was concomitantly delivered to the lumpectomy cavity, total dose 5Gy. Toxicity was assessed at the end of radiation therapy and at 3, 6, and 12 months using the RTOG/EORTC toxicity scale. Cosmetic results were assessed in agreement with the Harvard criteria. RESULTS: Median follow-up was 31 months, 74% showed grade 0-1 skin toxicity, 20% grade 2, and 6% grade 3. At 3 months of follow-up, grade 0 skin toxicity was observed in 51% of cases; grade 1 in 36%, and grade 2 in 13%. At 6 months, late skin and subcutaneous tissue toxicities were scored as grade 0 in 71%, grade 1 in 18%, and grade 2 in 11% of patients. At 1 year almost all the patients showed grade 0-1 skin toxicity. 97% of patients showed excellent or good cosmetic results. CONCLUSIONS: Accelerated hypofractionated radiotherapy for early breast cancer with concomitant electron boost seems to be feasible providing consistent clinical results with acceptable toxicity profile.

Concurrent Chemoradiation with Concomitant Boost in Locally Advanced Rectal Cancer: A Phase II Study.

AIM: The aim of this study was to evaluate the pathological response of locally advanced rectal cancer after preoperative concurrent two-drug chemotherapy and intensified radiation therapy (RT) with concomitant boost. PATIENTS AND METHODS: Patients with T4 tumor or local recurrence were included. A trial based on two-stage Simon's design was planned. RT was performed with 3D-conformal technique. The dose to the mesorectum and pelvic lymph nodes was 45 Gy (1.8 Gy/fraction). A concomitant boost was delivered to Gross Tumor Volume (GTV) 2 cm margin to a total dose of 55 Gy (2.2 Gy/fraction). The following concurrent chemotherapy was administered: Raltitrexed (3 mg/m(2)) and oxaliplatin (130 mg/m(2)) on days 1, 17, and 35 of RT. Pathological response was evaluated according to the Mandard classification. Toxicities were scored according to the Common Terminology Criteria for Adverse Events v3.0 scale. RESULTS: Eighteen patients (median age=64.5 years) were enrolled. The median follow-up was 22 months (range=2-36 months). After chemoradiation treatment, 16 patients underwent surgical resection (seven anterior resections and nine abdominal-perineal amputation); two patients did not undergo surgery due to early metastatic progression or refusal. R0 resection was achieved in all patients who underwent surgery. Five patients had pathological complete response [27.7%; 95% confidence interval (CI)=9.7-53.5%] and two patients showed only microscopic residual disease (11.1%; 95% CI=0.1-34.7%). Mandard grades 1 and 2 were detected in seven patients (38.9%; 95% CI=17.3-64.3%). Acute grade 3 or more toxicity was found in eight patients (44.4%; 95% CI=21.5-69.2%): one leucopenia-neutropenia, one liver, one skin and five cases of gastrointestinal toxicities. No patient had local tumor recurrence. One-, 2- and 3-year cumulative disease-free survival were 93.8%. One-, 2- and 3-year cumulative overall survival were 92.3%. CONCLUSION: Concurrent chemoradiation with concomitant boost in patients with advanced rectal cancer allows complete or near-complete pathological response in more than 38% of patients. However, severe acute toxicity was reported in more than one-third of patients.

Impact of tumour bed boost integration on acute and late toxicity in patients with breast cancer: A systematic review.

The purpose of this systematic review was to summarise the evidence from studies investigating the integration of tumour bed boosts into whole breast irradiation for patients with Stage 0-III breast cancer, with a focus on its impact on acute and late toxicities. A comprehensive systematic electronic search through the Ovid MEDLINE, EMBASE and PubMed databases from January 2000 to January 2015 was conducted. Studies were considered eligible if they investigated the efficacy of hypo- or normofractionated whole breast irradiation with the inclusion of a daily concurrent boost. The primary outcomes of interest were the degree of observed acute and late toxicity following radiotherapy treatment. Methodological quality assessment was performed on all included studies using either the Newcastle-Ottawa Scale or a previously published investigator-derived quality instrument. The search identified 35 articles, of which 17 satisfied our eligibility criteria. Thirteen and eleven studies reported on acute and late toxicities respectively. Grade 3 acute skin toxicity ranged from 1 to 7% whilst moderate to severe fibrosis and telangiectasia were both limited to 9%. Reported toxicity profiles were comparable to historical data at similar time-points. Studies investigating the delivery of concurrent boosts with whole breast radiotherapy courses report safe short to medium-term toxicity profiles and cosmesis rates. Whilst the quality of evidence and length of follow-up supporting these findings is low, sufficient evidence has been generated to consider concurrent boost techniques as an alternative to conventional sequential techniques.