Re-irradiation for intra-thoracic tumours and extra-thoracic breast cancer: dose accumulation, evaluation of efficacy and toxicity based on a literature review

British Journal of Radiology ◽

10.1259/bjr.20201292 ◽

2021 ◽

Author(s):

Dorota Gabrys ◽

Roland Kulik ◽

Agnieszka Namysł-Kaletka

Keyword(s):

Breast Cancer ◽

Overall Survival ◽

Local Control ◽

Treatment Time ◽

Late Toxicity ◽

Breast Conserving Therapy ◽

Published Data ◽

Overall Treatment Time ◽

Grade 3 ◽

Early Toxicity

The improvement seen in the diagnostic procedures and treatment of thoracic tumours means that patients have an increased chance of longer overall survival. Nevertheless, we can still find those who have had a recurrence or developed a secondary cancer in the previously treated area. These patients require retreatment including re-irradiation. We have reviewed the published data on thoracic re-irradiation which shows that some specific healthy tissues can tolerate a significant dose of irradiation and these patients benefit from aggressive treatment, however, there is a risk of damage to normal tissue under these circumstances. We analysed the literature data on re-irradiation in the areas of vertebral bodies, spinal cord, breast, lung and oesophagus. We evaluated the doses of primary and secondary radiotherapy, the treatment techniques, as well as the local control and median or overall survival in patients treated with re-radiation. The longest OS is reported in the case of re-irradiation after second breast-conserving therapy where the 5 year OS range is 81 to 100% and is shorter in patients with loco-reginal re-irradiation where the 5-y OS range is 18 to 60%. 2 year OS in patients re-irradiated for lung cancer and oesophagus cancer range from 13 to 74% and 18 to 42%, respectively. Majority grade ≥3 toxicity after second breast-conserving therapy was fibrosis up to 35%. For loco-regional breast cancer recurrences, early toxicity occurred in up to 33% of patients resulting in mostly desquamation, while late toxicity was recorded in up to 23% of patients and were mostly ulcerations. Early grade ≥3 lung toxicity developed in up to 39% of patients and up to 20% of Grade five hemoptysis. The most frequently observed early toxicity grade ≥3 in oesophageal cancer was oesophagitis recorded in up to 57% of patients, followed by hematological complications which was recorded in up to 50% of patients. The most common late complications included dysphagia, recorded in up to 16.7% of patients. We have shown that thoracic re-irradiation is feasible and effective in achieving local control in some patients. Re-irradiation should be performed with maximum accuracy and care using the best available treatment methods with a highly conformal, image-guided approach. Due to tremendous technological progress in the field of radiotherapy, we can deliver radiation precisely, shorten the overall treatment time and potentially reduce treatment-related toxicities.

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2006 Influence of overall treatment time on local control of breast cancer after radiotherapy alone

International Journal of Radiation Oncology*Biology*Physics ◽

10.1016/s0360-3016(99)90276-6 ◽

1999 ◽

Vol 45 (3) ◽

pp. 282

Author(s):

B.M. Dubray ◽

E. van Limbergen ◽

H.D. Thames ◽

W. van den Bogaert ◽

E. van des Schueren

Keyword(s):

Breast Cancer ◽

Local Control ◽

Treatment Time ◽

Overall Treatment Time ◽

Radiotherapy Alone

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Intensity-modulated radiation therapy (IMRT) for anal cancer: Results from a multi-institutional retrospective cohort study.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.e14555 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. e14555-e14555

Author(s):

Jason Andrew Call ◽

Brendan M Prendergast ◽

Lindsay G Jensen ◽

Celine B Ord ◽

Karyn A. Goodman ◽

...

Keyword(s):

Overall Survival ◽

Anal Cancer ◽

Local Control ◽

Treatment Time ◽

Intensity Modulated Radiation Therapy ◽

Late Toxicity ◽

Nodal Status ◽

Institutional Setting ◽

Severe Toxicity ◽

T Stage

e14555 Background: This study was done to assess the toxicity and efficacy of IMRT for anal cancer in a multi-institutional setting. Methods: Records of 152 total patients (pts) were reviewed retrospectively. Data on disease control and toxicity were collected as well as pt and treatment characteristics. Acute (<6 months) and late (>6 months) severe toxicity (grade >3) were recorded at each institution. Four were excluded for either presence of metastatic disease (2) or stage TX (2). There was data for late toxicity on 120 pts. Results: T stage was T1 in 28, T2 in 79, T3 in 29 and T4 in 12 pts. N stage was N0 in 77, N1 in 40, N2 in 19 and N3 in 12 pts. The median age was 56 yrs and median follow-up was 26.8 months. Cumulative IMRT dose was 51.25 Gy (median) (range: 4.32-61.2 Gy) in a median of 28 fractions (2-34). Chemotherapy was given in all but 2 pts and the most common regimen was 5- fluorouracil plus mitomycin-C. The median total elapsed treatment time was 40 days. Local control at 3 yrs was 87% and was significantly worse for patients with T3-4 disease (79% vs 90% at 3 years; p=0.04). There was no correlation between dose and local control. Regional control, distant control and overall survival were 97%, 91%, and 87% at 3 yrs, respectively. Nodal status was associated with regional and distal control as well as overall survival (p<0.01 for each). The most common acute severe toxicity was hematologic (41%). Severe acute GI, skin or other toxicity was 11%, 20% and 1% respectively. There were two grade 5 toxicities (hematologic and GI). Severe late toxicity was limited to skin (1%) and GI (3%). Conclusions: IMRT resulted in excellent local control in this multi-institutional cohort of pts. Although T stage did predict for worse local control, most pts with T3-4 disease were controlled with IMRT. Nodal status predicts for regional and distal control as well as overall survival. Severe toxicity was acceptable with this technique.

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Intensity-modulated radiation therapy (imrt) for anal cancer: Results from a multi-institutional retrospective cohort study.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.4_suppl.523 ◽

2013 ◽

Vol 31 (4_suppl) ◽

pp. 523-523 ◽

Cited By ~ 1

Author(s):

Jason Andrew Call ◽

Brendan M Prendergast ◽

Lindsay G Jensen ◽

Celine B Ord ◽

Karyn A. Goodman ◽

...

Keyword(s):

Overall Survival ◽

Anal Cancer ◽

Local Control ◽

Treatment Time ◽

Intensity Modulated Radiation Therapy ◽

Late Toxicity ◽

Nodal Status ◽

Institutional Setting ◽

Severe Toxicity ◽

T Stage

523 Background: This study was done to assess the toxicity and efficacy of IMRT for anal cancer in a multi-institutional setting. Methods: Records of 152 total patients (pts) were reviewed retrospectively. Data on disease control and toxicity were collected as well as pt and treatment characteristics. Acute (<6 months) and late (>=6 months) severe toxicity (grade >=3) were recorded at each institution. Four were excluded for either presence of metastatic disease (2) or stage TX (2). There was data for late toxicity on 120 pts. Results: T stage was T1 in 28, T2 in 79, T3 in 29 and T4 in 12 pts. N stage was N0 in 77, N1 in 40, N2 in 19 and N3 in 12 pts. The median age was 56 yrs and median follow-up was 26.8 months. Cumulative IMRT dose was 51.25 Gy (median) (range: 4.32-61.2 Gy) in a median of 28 fractions (2-34). Chemotherapy was given in all but 2 pts and the most common regimen was 5- fluorouracil plus mitomycin-C. The median total elapsed treatment time was 40 days. Local control at 3 yrs was 87% and was significantly worse for patients with T3-4 disease (79% vs 90% at 3 years; p=0.04). There was no correlation between dose and local control. Regional control, distant control and overall survival were 97%, 91%, and 87% at 3 yrs, respectively. Nodal status was associated with regional and distal control as well as overall survival (p<0.01 for each). The most common acute severe toxicity was hematologic (41%). Severe acute GI, skin or other toxicity was 11%, 20% and 1% respectively. There were two grade 5 toxicities (hematologic and GI). Severe late toxicity was limited to skin (1%) and GI (3%). Conclusions: IMRT resulted in excellent local control in this multi-institutional cohort of pts. Although T stage did predict for worse local control, most pts with T3-4 disease were controlled with IMRT. Nodal status predicts for regional and distal control as well as overall survival. Severe toxicity was acceptable with this technique.

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Outcomes after Radiation Therapy for HIV Positive Patients with Invasive Cervical Cancer

Cancer and Clinical Oncology ◽

10.5539/cco.v7n1p12 ◽

2018 ◽

Vol 7 (1) ◽

pp. 12 ◽

Cited By ~ 1

Author(s):

Victoire Molinier ◽

Florence Huguet ◽

Marcos Ballester ◽

Marina Karmochkine ◽

Christophe Hennequin ◽

...

Keyword(s):

Cervical Cancer ◽

Overall Survival ◽

Radiation Therapy ◽

Local Control ◽

Univariate Analysis ◽

Survival Rates ◽

Late Toxicity ◽

Hiv Positive ◽

Grade 3 ◽

Overall Survival Rates

Objective: To assess tolerance, local control, and survival outcomes for HIV (human immunodeficiency virus) positive patients with locally advanced cervical cancer (CC) treated with external beam radiation therapy (EBRT) and/or brachytherapy from an Assistance Publique - Hôpitaux de Paris (APHP) retrospective cohort.Methods: Between 2000 and 2014, 28 HIV positive patients presenting with a non-metastatic CC were treated in one of the five APHP radiation therapy centers. Fifteen patients (54%) underwent primary surgery. Twenty-four patients (88%) received EBRT, with concurrent chemotherapy in 22 cases, and 68% received brachytherapy.Results: The median follow-up was 58 months. At 5 years, local control (LCR) and overall survival rates (OS) were 56% and 46.5% respectively. A grade 3-4 acute toxicity (mainly hematological toxicity) was reported in 18 patients (64%). In univariate analysis, total irradiation dose (p=0.03) and cisplatin-based chemotherapy (p=0.005) were predictive of acute toxicity. A grade 3-4 late toxicity (mainly gastro-intestinal and renal) was observed in 7 patients (25%). In univariate analysis, HIV stage at diagnosis (p=0.02) and an initial CD4 count <200/mm3 (p=0.03) were predictive factors of late toxicity.Conclusion: In this study including HIV positive patients with CC, local control and overall survival rates seemed to be lower than those reported in the literature for non-HIV patients. We also reported an increase in acute and late toxicity, mainly hematological, underlying the fundamental role of immunosuppression in tolerance to radiation therapy.

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Prolonged Overall Treatment Time Negatively Affects the Outcomes of Stereotactic Body Radiotherapy for Early-Stage Non-Small Cell Lung Cancer: A Propensity Score-Weighted, Single-Center Analysis

10.21203/rs.3.rs-100183/v1 ◽

2020 ◽

Author(s):

TOSHIKI IKAWA ◽

Takahiro Tabuchi ◽

Koji Konishi ◽

Masahiro Morimoto ◽

Takero Hirata ◽

...

Keyword(s):

Overall Survival ◽

Propensity Score ◽

Local Control ◽

Treatment Time ◽

Early Stage ◽

Small Cell ◽

Tumor Control ◽

Small Cell Lung ◽

Overall Treatment Time ◽

Early Stage Nsclc

Abstract BackgroundPrevious studies have reported conflicting results for the effect of overall treatment time (OTT) on tumor control with stereotactic body radiotherapy (SBRT) for early-stage non-small cell lung cancer (NSCLC). To examine this effect, we conducted a propensity score-weighted, retrospective, observational study at a single institution.MethodsWe analyzed the data of 200 patients with early-stage NSCLC who underwent SBRT (48 Gy in 4 fractions) at our institution between January 2007 and October 2013. Patients were grouped into consecutive (OTT = 4–5 days, n = 116) or non-consecutive treatment groups (OTT = 6–10 days, n = 84). The outcomes of interest were local control and overall survival. The Cox regression model was used with propensity score and inverse probability of treatment weighting.ResultsThe median OTTs in the consecutive and non-consecutive groups were 4 and 6 days, respectively. The 5-year local control and overall survival rates in the consecutive group vs. non-consecutive group were 86.3% vs. 77.2% and 55.5% vs. 51.8%, respectively. After propensity score-weighting, consecutive SBRT was associated with positive local control (adjusted hazard ratio 0.30, 95% confidence interval 0.14–0.65; p=0.002) and overall survival benefits (adjusted hazard ratio 0.56, 95% confidence interval 0.34–0.91; p=0.019). ConclusionsProlonged OTT negatively affected the outcomes of patients with early-stage NSCLC treated with SBRT. To our knowledge, this is the first study to show that in patients with early-stage NSCLC treated with the same dose-fractionation regimen, consecutive SBRT has a more beneficial effect on tumor control than does non-consecutive SBRT.

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Proton Therapy for Major Salivary Gland Cancer: Clinical Outcomes

International Journal of Particle Therapy ◽

10.14338/ijpt-20-00044.1 ◽

2021 ◽

Vol 8 (1) ◽

pp. 261-272

Author(s):

Alexander N. Hanania ◽

Xiaodong Zhang ◽

G. Brandon Gunn ◽

David I. Rosenthal ◽

Adam S. Garden ◽

...

Keyword(s):

Overall Survival ◽

Salivary Gland ◽

Proton Beam ◽

Local Control ◽

Proton Therapy ◽

Late Toxicity ◽

Proton Beam Therapy ◽

Major Salivary Gland ◽

Grade 3

Abstract Purpose To report clinical outcomes in terms of disease control and toxicity in patients with major salivary gland cancers (SGCs) treated with proton beam therapy. Materials and Methods Clinical and dosimetric characteristics of patients with SGCs treated from August 2011 to February 2020 on an observational, prospective, single-institution protocol were abstracted. Local control and overall survival were calculated by the Kaplan-Meier method. During radiation, weekly assessments of toxicity were obtained, and for patients with ≥ 90 days of follow-up, late toxicity was assessed. Results Seventy-two patients were identified. Median age was 54 years (range, 23-87 years). Sixty-three patients (88%) received postoperative therapy, and nine patients (12%) were treated definitively. Twenty-six patients (36%) received concurrent chemotherapy. Nine patients (12%) had received prior radiation. All (99%) but one patient received unilateral treatment with a median dose of 64 GyRBE (relative biological effectiveness) (interquartile range [IQR], 60-66), and 53 patients (74%) received intensity-modulated proton therapy with either single-field or multifield optimization. The median follow-up time was 30 months. Two-year local control and overall survival rates were 96% (95% confidence interval [CI] 85%-99%) and 89% (95% CI 76%-95%], respectively. Radiation dermatitis was the predominant grade-3 toxicity (seen in 21% [n = 15] of the patients), and grade ≥ 2 mucositis was rare (14%; n = 10 patients). No late-grade ≥ 3 toxicities were reported. Conclusion Proton beam therapy for treatment of major SGCs manifests in low rates of acute mucosal toxicity. In addition, the current data suggest a high rate of local control and minimal late toxicity.

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Mastectomy or Breast-Conserving Therapy for Early Breast Cancer in Real-Life Clinical Practice: Outcome Comparison of 7565 Cases

Cancers ◽

10.3390/cancers11020160 ◽

2019 ◽

Vol 11 (2) ◽

pp. 160 ◽

Cited By ~ 13

Author(s):

Stefanie Corradini ◽

Daniel Reitz ◽

Montserrat Pazos ◽

Stephan Schönecker ◽

Michael Braun ◽

...

Keyword(s):

Breast Cancer ◽

Overall Survival ◽

Local Control ◽

Early Stage ◽

Multivariable Analysis ◽

Real Life ◽

Radical Mastectomy ◽

Breast Conserving Therapy ◽

Free Survival

Although the organ preservation strategy by breast-conserving surgery (BCS) followed by radiation therapy (BCT) has revolutionized the treatment approach of early stage breast cancer (BC), the choice between treatment options in this setting can still vary according to patient preferences. The aim of the present study was to compare the oncological outcome of mastectomy versus breast-conserving therapy in patients treated in a modern clinical setting outside of clinical trials. 7565 women diagnosed with early invasive BC (pT1/2pN0/1) between 1998 and 2014 were included in this study (median follow-up: 95.2 months). In order to reduce selection bias and confounding, a subgroup analysis of a matched 1:1 case-control cohort consisting of 1802 patients was performed (median follow-up 109.4 months). After adjusting for age, tumor characteristics and therapies, multivariable analysis for local recurrence-free survival identified BCT as an independent predictor for improved local control (hazard ratio [HR]:1.517; 95%confidence interval:1.092–2.108, p = 0.013) as compared to mastectomy alone in the matched cohort. Ten-year cumulative incidence (CI) of lymph node recurrences was 2.0% following BCT, compared to 5.8% in patients receiving mastectomy (p < 0.001). Similarly, 10-year distant-metastasis-free survival (89.4% vs. 85.5%, p = 0.013) was impaired in patients undergoing mastectomy alone. This translated into improved survival in patients treated with BCT (10-year overall survival (OS) estimates 85.3% vs. 79.3%, p < 0.001), which was also significant on multivariable analysis (p = 0.011). In conclusion, the present study showed that patients treated with BCS followed by radiotherapy had an improved outcome compared to radical mastectomy alone. Specifically, local control, distant control, and overall survival were significantly better using the conservative approach. Thus, as a result of the present study, physicians should encourage patients to receive BCS with radiotherapy rather than mastectomy, whenever it is medically feasible and appropriate.

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Altered Fractionation Schedules in Radiotherapy of Head and Neck Cancer. A Review

Tumori Journal ◽

10.1177/030089169207800506 ◽

1992 ◽

Vol 78 (5) ◽

pp. 311-325 ◽

Cited By ~ 7

Author(s):

Carlo Fallai ◽

Patrizia Olmi

Keyword(s):

Total Dose ◽

Head And Neck ◽

Local Control ◽

Randomized Trials ◽

Treatment Time ◽

Dose Intensity ◽

Field Size ◽

Overall Treatment Time ◽

Altered Fractionation ◽

Improvement In Survival

The authors review the main contributions of international literature to show the current status in clinical trials on unconventional fractionations of the dose in radiotherapy of head and neck cancers. Several clinical (but only a few randomized) trials have been conducted over the last 15 years using hyperfractionated (HF), accelerated (AF) or mixed (HF-AF) schedules. HF schedules have obtained promising results in terms of local control in comparison with conventional fractionation (CF) of the dose. Improvement in survival was also obtained by the random trials of Pinto and Sanchiz, whereas in EORTC trial no. 22791, the improvement in survival rate was only marginal. A significant increase in local control and, less frequently, in survival has been claimed in several studies using HF-AF. Such data still need to be confirmed by a random study, since EORTC trial 22811 showed superimposable results in comparison with CF. Selection of the most suitable cases for altered fractionation schemes is also being studied in ongoing trials of the EORTC (22851) and RTOG (90-03). As regards acute reactions during and after altered fractionation, they are more severe than after CF. Only pure HF with a dose intensity approximately comparable to CF seems to produce similar acute reactions. Several factors have been found to influence the severity of acute mucosal reactions: interfraction interval, overall treatment time, total dose, and field size. As regards late damage, genuine HF schemes seem to cause roughly equivalent late damage in comparison to CF, whereas high-dose intensity schedules have a higher rate of complications. Interfraction interval, overall treatment time, total dose, fraction size and field size can influence the risk of late sequelae. Before altered fractionations can be considered standard therapy, more data are needed, which should be provided by multicentric randomized trials, some of which are already in progress.

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Phase III Trial of Epirubicin Plus Paclitaxel Compared With Epirubicin Plus Cyclophosphamide As First-Line Chemotherapy for Metastatic Breast Cancer: United Kingdom National Cancer Research Institute Trial AB01

Journal of Clinical Oncology ◽

10.1200/jco.2005.01.1817 ◽

2005 ◽

Vol 23 (33) ◽

pp. 8322-8330 ◽

Cited By ~ 44

Author(s):

Ruth E. Langley ◽

James Carmichael ◽

Alison L. Jones ◽

David A. Cameron ◽

Wendi Qian ◽

...

Keyword(s):

Breast Cancer ◽

Overall Survival ◽

Metastatic Breast Cancer ◽

Survival Time ◽

Metastatic Breast ◽

Progression Free Survival ◽

First Line ◽

Free Survival ◽

Grade 3 ◽

Line Chemotherapy

Purpose To compare the effectiveness and tolerability of epirubicin and paclitaxel (EP) with epirubicin and cyclophosphamide (EC) as first-line chemotherapy for metastatic breast cancer (MBC). Patients and Methods Patients previously untreated with chemotherapy (except for adjuvant therapy) were randomly assigned to receive either EP (epirubicin 75 mg/m2 and paclitaxel 200 mg/m2) or EC (epirubicin 75 mg/m2 and cyclophosphamide 600 mg/m2) administered intravenously every 3 weeks for a maximum of six cycles. The primary outcome was progression-free survival; secondary outcome measures were overall survival, response rates, and toxicity. Results Between 1996 and 1999, 705 patients (353 EP patients and 352 EC patients) underwent random assignment. Patient characteristics were well matched between the two groups, and 71% of patients received six cycles of treatment. Objective response rates were 65% for the EP group and 55% for the EC group (P = .015). At the time of analysis, 641 patients (91%) had died. Median progression-free survival time was 7.0 months for the EP group and 7.1 months for the EC group (hazard ratio = 1.07; 95% CI, 0.92 to 1.24; P = .41), and median overall survival time was 13 months for the EP group and 14 months for the EC group (hazard ratio = 1.02; 95% CI, 0.87 to 1.19; P = .8). EP patients, compared with EC patients, had more grade 3 and 4 mucositis (6% v 2%, respectively; P = .0006) and grade 3 and 4 neurotoxicity (5% v 1%, respectively; P < .0001). Conclusion In terms of progression-free survival and overall survival, there was no evidence of a difference between EP and EC. The data demonstrate no additional advantage to using EP instead of EC as first-line chemotherapy for MBC in taxane-naïve patients.

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