Research ArticleClinical Studies
Open Access

Radiation Dermatitis and Pneumonitis in Patients Irradiated for Breast Cancer

MARIE C. EGGERT, NATHAN Y. YU and DIRK RADES
In Vivo November 2023, 37 (6) 2654-2661; DOI: https://doi.org/10.21873/invivo.13374

Abstract

Background/Aim: Adjuvant radiotherapy (RT) for breast cancer can be associated with acute dermatitis (ARD) and pneumonitis (RP). Prevalence and risk factors were characterized. Patients and Methods: This study included 489 breast cancer patients receiving adjuvant RT with conventional fractionation (CF) ± sequential or simultaneous integrated boost, or hypo-fractionation ± sequential boost. RT-regimen and 15 characteristics were investigated for grade ≥2 ARD and RP. Results: Prevalence of grade ≥2 ARD and RP was 25.3% and 2.5%, respectively. On univariate analyses, ARD was significantly associated with CF and radiation boost (p<0.0001), age ≤60 years (p=0.008), Ki-67 ≥15% (p=0.012), and systemic treatment (p=0.002). On multivariate analysis, RT-regimen (p<0.0001) and age (p=0.009) were associated with ARD. Chronic inflammatory disease was significantly associated with RP on univariate (p=0.007) and multivariate (p=0.016) analyses. Conclusion: Risk factors for grade ≥2 ARD and RP were determined that may help identify patients who require closer monitoring during and after RT.

Key Words:

Breast cancer is the most common cancer type in females in Western countries (1, 2). Many of these women with non-metastatic disease receive breast conserving surgery or mastectomy followed by local or loco-regional irradiation (3, 4). Adjuvant radiotherapy (RT) may be associated with adverse events including acute radiation dermatitis (ARD) and radiation pneumonitis (RP) (5, 6). ARD was reported to have a negative impact on the patients’ quality of life, and RP can even be fatal (7, 8). In the literature, the prevalence of clinically relevant grade ≥2 ARD ranges between 3% and 76%, with higher rates in patients treated with conventional fractionation (CF) than in patients receiving hypofractionation (HF) (9-26). ARD usually develops during the second to third week of radiotherapy, becomes more severe during the further RT-course and possibly the first post-RT week, and disappears a few weeks after completion of RT (5). In contrast, RP is considered a subacute effect of RT, which often develops only several weeks or months following RT (6). The prevalence of RP after RT of breast cancer ranges between 0.8% and 19.6% (6, 10, 27-33). Considering the comparably wide ranges regarding the prevalence of ARD and RP, it becomes obvious that additional studies are required to more precisely define the prevalence of these two RT-related side effects in breast cancer patients. Our present study evaluated the prevalence in a cohort of breast cancer patients irradiated between 2016 and 2019. Moreover, it aimed to determine risk factors for ARD and RP, in order to contribute to early identification of patients at risk who would benefit from closer monitoring of adverse events during and after the RT-course.

Patients and Methods

The present retrospective study investigated grade ≥2 ARD and grade ≥2 RP in 489 female breast cancer patients treated with adjuvant radiotherapy between 2016 and 2019. The original study protocol and an amendment were approved by the ethics committee of the University of Lübeck, Germany (file numbers 21-088 and 2023-538_1).

The patients were irradiated after breast conserving surgery (n=462) or mastectomy (n=27). Eight patients had bilateral and 481 patients had unilateral cancer. Of the latter group, 65 patients had ductal or lobular carcinoma in situ (Tis). Of the 416 patients with invasive cancers, primary tumor stage was T1 in 267 patients, T2 in 131 patients, T3 in 12 patients, and T4 in eight patients. Lymph nodes were negative (N0) in 345 of these 416 patients, N1mi (micro-metastatic stage=intra-nodal cancer between >0.2 and ≤2 mm) in eight patients, and positive in 63 patients. Of the eight patients with bilateral breast cancer, primary tumor distributions were Tis and Tis in one patient, Tis and T1 in one patient, Tis and T3 in one patient, T1 and T1 in one patient, T1 and T2 in two patients, and T2 and T2 in two patients. In the seven patients with invasive cancer, lymph nodes were bilaterally negative in four patients and positive on one side in three patients.

Radiotherapy was mainly performed with intensity-modulated radiation therapy (IMRT) or volumetric-modulated arc therapy (VMAT) using 6 MV photon beams. Treatment volumes included whole breast alone in 437 patients, chest wall alone in eight patients, whole breast plus regional lymph nodes in 25 patients, and chest wall plus regional lymph nodes in 19 patients. Dose-fractionation regimens included conventional fractionation (CF) with 50.4 Gy in 28 fractions of 1.8 Gy over 5.5 weeks in 344 patients and hypo-fractionation (HF) with 40 Gy in 15 fractions of 2.67 Gy over 3 weeks in 245 patients. Of the patients treated with CF, 117 patients received a sequential boost (SEB) and 59 patients a simultaneous integrated boost (SIB) to the primary tumor bed. Of the patients treated with HF, 164 patients received a SEB. The deep-inspiration breath hold (DIBH) technique was used in 242 patients, mainly (n=212) for left-sided breast cancer.

In addition to the radiation regimen (CF without boost vs. CF+SEB vs. CF+SIB vs. HF without boost vs. HF+SEB), 14 characteristics (Table I) were evaluated for potential associations with grade ≥2 ARD according to Common Terminology Criteria of Adverse Events (CTCAE) version 5.0 (34). These characteristics included age (≤60 vs. ≥61 years), primary tumor stage [carcinoma in situ (Tis) vs. invasive cancer (T1-4)], nodal stage (N0 or N1mi vs. N1-3), histologic grading (G1-2 vs. G3), hormone receptor status (negative vs. positive), Ki-67 labeling index (≤15% vs. >15%), side of affected breast (right vs. left vs. bilateral), main tumor site [outer quadrant vs. inner quadrant vs. central vs. other (not clear, multiple sites)], radiotherapy of lymph nodes in addition to whole breast or chest wall (no vs. yes), irradiation with DIBH technique (no vs. yes), systemic treatment (chemotherapy, immunotherapy, or endocrine therapy) before and/or during the radiotherapy course (no vs. yes), history of hypertension (no vs. yes), history of diabetes mellitus (no vs. yes), and history of chronic inflammatory disease (no vs. yes). “Chronic inflammatory diseases” included mainly bronchial asthma (n=27) and rheumatoid arthritis (n=14), but also psoriasis, neurodermitis, fibrosing alveolitis, sarcoidosis, Crohn’s disease, ulcerative colitis, Hashimoto’s thyroiditis, systemic lupus erythematosus, and dermatomyositis. Fifteen characteristics (Table I) were evaluated for potential associations with grade ≥2 RP. These included those 14 characteristics evaluated for ARD plus the mean radiation dose to ipsilateral lung (≤7 Gy vs. >7 Gy). Four hundred and eighty nine and 487 patients, respectively, were evaluable for grade ≥2 RP and grade ≥2 ARD. Median time of follow up was 43 months (range=10-77 months) following RT.

View this table:
Table I.

Distribution of the investigated characteristics.

Univariate analyses were performed with the Chi-square test (number of patients ≥5 in all subgroups) or the Fisher’s exact test. For the multivariate analyses, a logistic regression model was used that included the factors with p-values <0.20 on univariate analyses. Statistical analyses were performed with the SAS software, version 9.4 (SAS, Cary, NC, USA). p-Values <0.05 indicated significance and p-values <0.10 a trend.

Results

In the entire cohort, 123 of 487 patients (25.3%) experienced grade ≥2 ARD. On univariate analyses, grade ≥2 ARD was significantly associated with conventionally fractionated RT (p<0.0001), particularly with CF+SEB or CF+SIB, age ≤60 years (p=0.008), Ki-67 labeling index ≥15% (p=0.012), and systemic treatment before and/or during the course of RT (p=0.002) (Table II). In additional analyses comparing RT-regimens, grade ≥2 ARD was significantly more common in patients treated with CF vs. HF (37.9% vs. 12.7%, p<0.0001), and in patients receiving a radiation boost (SEB or SIB) vs. no boost (30.4% vs. 13.5%, p<0.0001). Moreover, trends for associations with grade ≥2 ARD were found for invasive cancers (p=0.097), less differentiated (G3)-tumors (p=0.073), and history of chronic inflammatory disease (p=0.096). In the subsequent multivariate analysis (Table III), the RT-regimen (p<0.0001) and age ≤60 years (p=0.009) were significantly associated with grade ≥2 ARD. In the entire series, 12 of 489 patients (2.5%) developed grade ≥2 RP after median 11.25 weeks (range=0-17 weeks) following RT. History of chronic inflammatory disease was significantly associated with grade ≥2 RP on univariate (p=0.007, Table IV) and multivariate (p=0.016, Table V) analyses. The prevalence of grade ≥2 RP was 2.5% (6 of 244 patients) after CF and 2.4% (6 of 245 patients) after HF, respectively (p=0.99).

View this table:
Table II.

Associations between investigated characteristics and acute radiation dermatitis grade ≥2 (univariate analysis, n=487).

View this table:
Table III.

Multivariate analysis with respect to acute radiation dermatitis grade ≥2.

View this table:
Table IV.

Associations between investigated characteristics and radiation pneumonitis grade ≥2 (univariate analysis, n=489).

View this table:
Table V.

Multivariate analysis with respect to radiation pneumonitis grade ≥2.

Discussion

Adjuvant RT for breast cancer can lead to side effects that may significantly impair the patients’ quality of life (7). ARD is the most common toxicity occurring during the course of RT or shortly afterwards (5). In previous studies, the prevalence of grade ≥2 ARD ranged between 3% and 76% (9-26). Considering this wide range, additional studies are needed. For adequate personalized counseling, identifying risk factors regarding the probability of grade ≥2 ARD and RP is valuable. RP can be serious and difficult to diagnose and often occurs several weeks or months following RT (35, 36). Therefore, it is important to identify patients who are at risk of developing grade ≥2 RP.

The current study aimed to help define the prevalence of grade ≥2 ARD and RP in breast cancer patients treated with adjuvant RT. In our study, the prevalence of grade ≥2 ARD was 25.3%, which was well in the range of 3-76% reported in the literature (9-24). In those studies that state the prevalence of grade ≥2 ARD irrespective of the type of fractionation, ARD rates ranged between 17% and 63% (11, 20-23, 26). The prevalence of grade ≥2 ARD was <20% in one of seven studies, 20-30% in four studies (including our present study), and >30% in two studies (11, 20-23, 26). In patients receiving CF, the prevalence of grade ≥2 ARD in our study was 37.9%, which was in the range of 11-76% found in previous studies (9, 10, 12-18). The prevalence of ARD after receiving CF was <20% in three studies, 20-40% in four studies (including our present study), and >40% (i.e. >50%) in three studies, respectively (9, 10, 12-18). In patients receiving HF, the prevalence of grade ≥2 ARD was 12.7% in our study, which was well in the range of 3-38% observed in other studies (9, 12, 14-17, 19, 24). The prevalence of grade ≥2 ARD in patients receiving HF was <10% in one of nine studies, 10-30% in seven studies (including our present study), and >30% in one study, respectively.

The probability of developing grade ≥2 ARD is increased if patients have certain risk factors. According to the results of the present study, CF (vs. HF), a radiation boost, age ≤60 years, Ki-67 labeling index ≥15%, and systemic treatment before and/or during the course of RT-course were associated with an increased risk of grade ≥2 ARD. Some of these factors, namely CF, addition of a boost, age ≤60 years, and systemic treatment were described also in previous studies (5, 9, 12, 14-18, 26, 37-42). In contrast, the association between higher Ki-67 labeling index and increased risk of grade ≥2 ARD requires further investigation. It has already been shown that a higher Ki-67 labeling index was associated with better response to neoadjuvant chemotherapy for breast cancer and better response to RT for small-cell lung cancer (43-46). However, it is not clear whether an increased radio-sensitivity of the tumor cells also means a greater radio-sensitivity of the normal tissue associated with more pronounced toxicities.

In the entire cohort of the present study, the prevalence of grade ≥2 RP was 2.5%, which was in the range of 0.8-19.6% reported by other authors (6, 10, 12, 20, 27-33). In six studies and a systematic review, the rates of RP were ≤4.0%, and in four studies >4.0%.

In our study, the type of fractionation had no significant impact on the prevalence of grade ≥2 RP. This finding is consistent with the results of the meta-analysis and systematic review performed by Liu et al. (47). In that study, no significant difference was found between CF and HF following mastectomy regarding the occurrence of acute lung toxicity (odds ratio=0.94; 95% confidence interval=0.74-1.20, p=0.62). In contrast to the type of fractionation, history of chronic inflammatory disease was significantly associated with grade ≥2 RP on both univariate and multivariate analyses. This result is consistent with our previous study, where chronic inflammatory disease was common in patients developing symptomatic RP (6). Moreover, in the prospective study of Vasiljevic et al., previous pneumonia promoted RP (32). In our present study, the two most common types of chronic inflammatory disease were bronchial asthma and rheumatoid arthritis. Associations with RP may be explained by the fact that bronchial asthma is a chronic inflammatory lung disease and rheumatoid arthritis can also affect the lungs (48, 49). When interpreting the results of the present study, its retrospective design including the risk of hidden selection biases need to be considered. The results should be confirmed in prospective trials. Moreover, additional studies appear reasonable that consider and compare RT-regimens, e.g. different types of fractionation and radiation boosts.

In summary, the study contributed to a more precise characterization of the prevalence of grade ≥2 ARD and RP in patients irradiated for breast cancer, which may be helpful during informed consent discussions. Moreover, risk factors for both adverse events were determined that can help identify patients who require closer monitoring during and after their RT-course. Confirmation of our results in prospective trials is warranted.

Footnotes

  • Authors’ Contributions

    M.C.E., N.Y.Y. and D.R. participated in the design of the study. M.C.E. collected the data that were analyzed by a professional statistician. D.R. drafted the article, which was reviewed and finally approved by all Authors.

  • Conflicts of Interest

    The Authors state that there are no conflicts of interest related to this study.

  • Received July 21, 2023.
  • Revision received August 28, 2023.
  • Accepted August 29, 2023.

This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY-NC-ND) 4.0 international license (https://creativecommons.org/licenses/by-nc-nd/4.0).

References

  1. ↵
    1. Siegel RL,
    2. Miller KD,
    3. Wagle NS,
    4. Jemal A
    : Cancer statistics, 2023. CA Cancer J Clin 73(1): 17-48, 2023. DOI: 10.3322/caac.21763
    OpenUrlCrossRefPubMed
  2. ↵
    1. Sung H,
    2. Ferlay J,
    3. Siegel RL,
    4. Laversanne M,
    5. Soerjomataram I,
    6. Jemal A,
    7. Bray F
    : Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 71(3): 209-249, 2021. DOI: 10.3322/caac.21660
    OpenUrlCrossRefPubMed
  3. ↵
    1. Early Breast Cancer Trialists’ Collaborative Group (EBCTCG),
    2. Darby S,
    3. McGale P,
    4. Correa C,
    5. Taylor C,
    6. Arriagada R,
    7. Clarke M,
    8. Cutter D,
    9. Davies C,
    10. Ewertz M,
    11. Godwin J,
    12. Gray R,
    13. Pierce L,
    14. Whelan T,
    15. Wang Y,
    16. Peto R
    : Effect of radiotherapy after breast-conserving surgery on 10-year recurrence and 15-year breast cancer death: meta-analysis of individual patient data for 10,801 women in 17 randomised trials. Lancet 378(9804): 1707-1716, 2011. DOI: 10.1016/S0140-6736(11)61629-2
    OpenUrlCrossRefPubMed
  4. ↵
    1. EBCTCG (Early Breast Cancer Trialists’ Collaborative Group),
    2. McGale P,
    3. Taylor C,
    4. Correa C,
    5. Cutter D,
    6. Duane F,
    7. Ewertz M,
    8. Gray R,
    9. Mannu G,
    10. Peto R,
    11. Whelan T,
    12. Wang Y,
    13. Wang Z,
    14. Darby S
    : Effect of radiotherapy after mastectomy and axillary surgery on 10-year recurrence and 20-year breast cancer mortality: meta-analysis of individual patient data for 8135 women in 22 randomised trials. Lancet 383(9935): 2127-2135, 2014. DOI: 10.1016/S0140-6736(14)60488-8
    OpenUrlCrossRefPubMed
  5. ↵
    1. Xie Y,
    2. Wang Q,
    3. Hu T,
    4. Chen R,
    5. Wang J,
    6. Chang H,
    7. Cheng J
    : Risk factors related to acute radiation dermatitis in breast cancer patients after radiotherapy: a systematic review and meta-analysis. Front Oncol 11: 738851, 2021. DOI: 10.3389/fonc.2021.738851
    OpenUrlCrossRefPubMed
  6. ↵
    1. Werner EM,
    2. Eggert MC,
    3. Bohnet S,
    4. Rades D
    : Prevalence and characteristics of pneumonitis following irradiation of breast cancer. Anticancer Res 39(11): 6355-6358, 2019. DOI: 10.21873/anticanres.13847
    OpenUrlAbstract/FREE Full Text
  7. ↵
    1. Fuzissaki MA,
    2. Paiva CE,
    3. Oliveira MA,
    4. Lajolo Canto PP,
    5. Paiva Maia YC
    : The impact of radiodermatitis on breast cancer patients’ quality of life during radiotherapy: a prospective cohort study. J Pain Symptom Manage 58(1): 92-99.e1, 2019. DOI: 10.1016/j.jpainsymman.2019.03.017
    OpenUrlCrossRef
  8. ↵
    1. Verma V,
    2. Simone CB 2nd.,
    3. Werner-Wasik M
    : Acute and late toxicities of concurrent chemoradiotherapy for locally-advanced non-small cell lung cancer. Cancers (Basel) 9(9): 120, 2017. DOI: 10.3390/cancers9090120
    OpenUrlCrossRefPubMed
  9. ↵
    1. Kawaguchi H,
    2. Tsujino K,
    3. Miki M,
    4. Matsumoto Y,
    5. Ota Y,
    6. Hirokaga K,
    7. Takao S,
    8. Soejima T,
    9. Sasaki R
    : Patient preference study comparing hypofractionated versus conventionally fractionated whole-breast irradiation after breast-conserving surgery. Jpn J Clin Oncol 49(6): 545-553, 2019. DOI: 10.1093/jjco/hyz003
    OpenUrlCrossRef
  10. ↵
    1. Abdeltawab AA,
    2. Ali SA,
    3. Mostafa HG,
    4. Hassan MA
    : Predictive factors increasing the risk of radiation toxicity in patients with early breast cancer. Asian Pac J Cancer Prev 22(1): 145-149, 2021. DOI: 10.31557/APJCP.2021.22.1.145
    OpenUrlCrossRef
  11. ↵
    1. Chen CH,
    2. Hsieh CC,
    3. Chang CS,
    4. Chen MF
    : A retrospective analysis of dose distribution and toxicity in patients with left breast cancer treated with adjuvant intensity-modulated radiotherapy: Comparison with three-dimensional conformal radiotherapy. Cancer Manag Res 12: 9173-9182, 2020. DOI: 10.2147/CMAR.S269893
    OpenUrlCrossRef
  12. ↵
    1. Akl FMF,
    2. Khater A
    : Hypofractionated versus conventionally fractionated radiotherapy in post-mastectomy breast cancer patients. J Cancer Ther 09(11): 941-954, 2018. DOI: 10.4236/jct.2018.911078
    OpenUrlCrossRef
    1. Pasquier D,
    2. Bataille B,
    3. Le Tinier F,
    4. Bennadji R,
    5. Langin H,
    6. Escande A,
    7. Tresch E,
    8. Darloy F,
    9. Carlier D,
    10. Crop F,
    11. Lartigau E
    : Correlation between toxicity and dosimetric parameters for adjuvant intensity modulated radiation therapy of breast cancer: a prospective study. Sci Rep 11(1): 3626, 2021. DOI: 10.1038/s41598-021-83159-3
    OpenUrlCrossRef
  14. ↵
    1. Tortorelli G,
    2. Di Murro L,
    3. Barbarino R,
    4. Cicchetti S,
    5. di Cristino D,
    6. Falco MD,
    7. Fedele D,
    8. Ingrosso G,
    9. Janniello D,
    10. Morelli P,
    11. Murgia A,
    12. Ponti E,
    13. Terenzi S,
    14. Tolu B,
    15. Santoni R
    : Standard or hypofractionated radiotherapy in the postoperative treatment of breast cancer: a retrospective analysis of acute skin toxicity and dose inhomogeneities. BMC Cancer 13: 230, 2013. DOI: 10.1186/1471-2407-13-230
    OpenUrlCrossRef
    1. Butler-Xu YS,
    2. Marietta M,
    3. Zahra A,
    4. TenNapel M,
    5. Mitchell M
    : The effect of breast volume on toxicity using hypofractionated regimens for early stage breast cancer for patients. Adv Radiat Oncol 4(2): 261-267, 2018. DOI: 10.1016/j.adro.2018.10.005
    OpenUrlCrossRef
    1. Karasawa K,
    2. Kunogi H,
    3. Hirai T,
    4. Hojo H,
    5. Hirowatari H,
    6. Izawa H,
    7. Ito K,
    8. Sasai K,
    9. Kawashima M,
    10. Furuya T,
    11. Sugimoto S,
    12. Kurokawa C,
    13. Ozawa S,
    14. Saito M
    : Comparison of hypofractionated and conventionally fractionated whole-breast irradiation for early breast cancer patients: a single-institute study of 1,098 patients. Breast Cancer 21(4): 402-408, 2014. DOI: 10.1007/s12282-012-0406-6
    OpenUrlCrossRef
  17. ↵
    1. Jagsi R,
    2. Griffith KA,
    3. Boike TP,
    4. Walker E,
    5. Nurushev T,
    6. Grills IS,
    7. Moran JM,
    8. Feng M,
    9. Hayman J,
    10. Pierce LJ
    : Differences in the acute toxic effects of breast radiotherapy by fractionation schedule. JAMA Oncol 1(7): 918, 2015. DOI: 10.1001/jamaoncol.2015.2590
    OpenUrlCrossRefPubMed
  18. ↵
    1. Ding J,
    2. Guo Y,
    3. Li Q,
    4. Chen J,
    5. Hu P,
    6. Liu Q,
    7. Cao Y,
    8. Wu J
    : The incidence of postoperative radiotherapy-induced acute dermatitis in breast cancer and its influencing factors for Chinese women. Onco Targets Ther 11: 1665-1670, 2018. DOI: 10.2147/OTT.S156066
    OpenUrlCrossRef
  19. ↵
    1. Ciammella P,
    2. Podgornii A,
    3. Galeandro M,
    4. Micera R,
    5. Ramundo D,
    6. Palmieri T,
    7. Cagni E,
    8. Iotti C
    : Toxicity and cosmetic outcome of hypofractionated whole-breast radiotherapy: predictive clinical and dosimetric factors. Radiat Oncol 9: 97, 2014. DOI: 10.1186/1748-717X-9-97
    OpenUrlCrossRefPubMed
  20. ↵
    1. Aoulad N,
    2. Massabeau C,
    3. de Lafontan B,
    4. Vieillevigne L,
    5. Hangard G,
    6. Ciprian C,
    7. Chaltiel L,
    8. Moyal E,
    9. Izar F
    : [Acute toxicity of breast cancer irradiation with modulated intensity by tomotherapy.] Cancer Radiother 21(3): 180-189, 2017. DOI: 10.1016/j.canrad.2016.11.008
    OpenUrlCrossRef
    1. Liu D,
    2. Zheng Z,
    3. Zhang S,
    4. Zhu C,
    5. Zhang H,
    6. Zhou Y
    : Analysis of risk factors related to acute radiation dermatitis in breast cancer patients during radiotherapy. J Cancer Res Ther 18(7): 1903, 2022. DOI: 10.4103/jcrt.jcrt_1203_22
    OpenUrlCrossRef
    1. Bruand M,
    2. Salleron J,
    3. Guihard S,
    4. Crety CM,
    5. Liem X,
    6. Pasquier D,
    7. Lamrani-Ghaouti A,
    8. Charra-Brunaud C,
    9. Peiffert D,
    10. Clavier JB,
    11. Desandes E,
    12. Faivre JC
    : Acute skin toxicity of conventional fractionated versus hypofractionated radiotherapy in breast cancer patients receiving regional node irradiation: the real-life prospective multicenter HYPOBREAST cohort. BMC Cancer 22(1): 1318, 2022. DOI: 10.1186/s12885-022-10402-z
    OpenUrlCrossRef
  23. ↵
    1. Freedman GM,
    2. Li T,
    3. Nicolaou N,
    4. Chen Y,
    5. Ma CC,
    6. Anderson PR
    : Breast intensity-modulated radiation therapy reduces time spent with acute dermatitis for women of all breast sizes during radiation. Int J Radiat Oncol Biol Phys 74(3): 689-694, 2009. DOI: 10.1016/j.ijrobp.2008.08.071
    OpenUrlCrossRefPubMed
  24. ↵
    1. De Santis MC,
    2. Bonfantini F,
    3. Di Salvo F,
    4. Fiorentino A,
    5. Riboldi VM,
    6. Di Cosimo S,
    7. Bianchi GV,
    8. Gennaro M,
    9. Cosentino V,
    10. Sant M,
    11. Pignoli E,
    12. Valdagni R,
    13. Lozza L
    : Trastuzumab and hypofractionated whole breast radiotherapy: a victorious combination? Clin Breast Cancer 18(3): e363-e371, 2018. DOI: 10.1016/j.clbc.2017.08.011
    OpenUrlCrossRef
    1. Xie Y,
    2. Hu T,
    3. Chen R,
    4. Chang H,
    5. Wang Q,
    6. Cheng J
    : Predicting acute radiation dermatitis in breast cancer: a prospective cohort study. BMC Cancer 23(1): 537, 2023. DOI: 10.1186/s12885-023-10821-6
    OpenUrlCrossRef
  26. ↵
    1. De Langhe S,
    2. Mulliez T,
    3. Veldeman L,
    4. Remouchamps V,
    5. van Greveling A,
    6. Gilsoul M,
    7. De Schepper E,
    8. De Ruyck K,
    9. De Neve W,
    10. Thierens H
    : Factors modifying the risk for developing acute skin toxicity after whole-breast intensity modulated radiotherapy. BMC Cancer 14: 711, 2014. DOI: 10.1186/1471-2407-14-711
    OpenUrlCrossRefPubMed
  27. ↵
    1. Epler GR,
    2. Kelly EM
    : Systematic review of postradiotherapy bronchiolitis obliterans organizing pneumonia in women with breast cancer. Oncologist 19(12): 1216-1226, 2014. DOI: 10.1634/theoncologist.2014-0041
    OpenUrlAbstract/FREE Full Text
    1. Sato H,
    2. Ebi J,
    3. Tamaki T,
    4. Yukawa A,
    5. Nakajima M,
    6. Ohtake T,
    7. Suzuki Y
    : Incidence of organizing pneumonia after whole-breast radiotherapy for breast cancer, and risk factor analysis. J Radiat Res 59(3): 298-302, 2018. DOI: 10.1093/jrr/rry001
    OpenUrlCrossRef
    1. Wen G,
    2. Tan YT,
    3. Lan XW,
    4. He ZC,
    5. Huang JH,
    6. Shi JT,
    7. Lin X,
    8. Huang XB
    : New clinical features and dosimetric predictor identification for symptomatic radiation pneumonitis after tangential irradiation in breast cancer patients. J Cancer 8(18): 3795-3802, 2017. DOI: 10.7150/jca.21158
    OpenUrlCrossRef
    1. Yu TK,
    2. Whitman GJ,
    3. Thames HD,
    4. Buzdar AU,
    5. Strom EA,
    6. Perkins GH,
    7. Schechter NR,
    8. Mcneese MD,
    9. Kau S,
    10. Thomas ES,
    11. Hortobagyi GN,
    12. Buchholz TA
    : Clinically relevant pneumonitis after sequential paclitaxel-based chemotherapy and radiotherapy in breast cancer patients. J Natl Cancer Inst 96(22): 1676-1681, 2004. DOI: 10.1093/jnci/djh315
    OpenUrlCrossRefPubMed
    1. Dörr W,
    2. Bertmann S,
    3. Herrmann T
    : Radiation induced lung reactions in breast cancer therapy. Strahlenther Onkol 181(9): 567-573, 2005. DOI: 10.1007/s00066-005-1457-9
    OpenUrlCrossRefPubMed
  32. ↵
    1. Vasiljevic D,
    2. Arnold C,
    3. Neuman D,
    4. Fink K,
    5. Popovscaia M,
    6. Kvitsaridze I,
    7. Nevinny-Stickel M,
    8. Glatzer M,
    9. Lukas P,
    10. Seppi T
    : Occurrence of pneumonitis following radiotherapy of breast cancer - A prospective study. Strahlenther Onkol 194(6): 520-532, 2018. DOI: 10.1007/s00066-017-1257-z
    OpenUrlCrossRefPubMed
  33. ↵
    1. Jeba J,
    2. Isiah R,
    3. Subhashini J,
    4. Backianathan S,
    5. Thangakunam B,
    6. Christopher DJ
    : Radiation pneumonitis after conventional radiotherapy for breast cancer: a prospective study. J Clin Diagn Res 9(7): XC01-XC05, 2015. DOI: 10.7860/JCDR/2015/13969.6211
    OpenUrlCrossRef
  34. ↵
    1. National Institutes of Health/National Cancer Institute
    : Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. National Institutes of Health/National Cancer Institute, 2017. Available at: https://ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/ctcae_v5_quick_reference_5x7.pdf [Last accessed on July, 31, 2023]
  35. ↵
    1. Rades D,
    2. Werner EM,
    3. Glatzel E,
    4. Eggert MC,
    5. Olbrich D,
    6. Tvilsted S,
    7. Bohnet S
    : Pneumonitis after radiotherapy for lung cancer (PARALUC): an interventional study to create a symptom-based scoring system for identification of patients developing radiation pneumonitis. BMC Cancer 20(1): 785, 2020. DOI: 10.1186/s12885-020-07291-5
    OpenUrlCrossRef
  36. ↵
    1. Rades D,
    2. Werner EM,
    3. Glatzel E,
    4. Bohnet S,
    5. Schild SE,
    6. Tvilsted SS,
    7. Janssen S
    : Early identification of pneumonitis in patients irradiated for lung cancer-final results of the PARALUC trial. Cancers (Basel) 15(2): 326, 2023. DOI: 10.3390/cancers15020326
    OpenUrlCrossRef
  37. ↵
    1. Arsenault J,
    2. Parpia S,
    3. Goldberg M,
    4. Rakovitch E,
    5. Reiter H,
    6. Doherty M,
    7. Lukka H,
    8. Sussman J,
    9. Wright J,
    10. Julian J,
    11. Whelan T
    : Acute toxicity and quality of life of hypofractionated radiation therapy for breast cancer. Int J Radiat Oncol Biol Phys 107(5): 943-948, 2020. DOI: 10.1016/j.ijrobp.2020.03.049
    OpenUrlCrossRef
    1. Yoshikawa N,
    2. Inomata T,
    3. Shimbo T,
    4. Takahashi M,
    5. Uesugi Y,
    6. Juri H,
    7. Narumi Y
    : Appropriate evaluation of and risk factors for radiation dermatitis in breast cancer patients receiving hypofractionated whole-breast irradiation after breast-conserving surgery. Breast Cancer 21(2): 170-176, 2014. DOI: 10.1007/s12282-012-0366-x
    OpenUrlCrossRef
    1. Behroozian T,
    2. Milton L,
    3. Li N,
    4. Zhang L,
    5. Lou J,
    6. Karam I,
    7. Wronski M,
    8. McKenzie E,
    9. Mawdsley G,
    10. Razvi Y,
    11. Chow E,
    12. Ruschin M
    : Predictive factors associated with radiation dermatitis in breast cancer. Cancer Treat Res Commun 28: 100403, 2021. DOI: 10.1016/j.ctarc.2021.100403
    OpenUrlCrossRef
    1. Joseph K,
    2. Vos LJ,
    3. Gabos Z,
    4. Pervez N,
    5. Chafe S,
    6. Tankel K,
    7. Warkentin H,
    8. Ghosh S,
    9. Amanie J,
    10. Powell K,
    11. Polkosnik LA,
    12. Horsman S,
    13. MacKenzie M,
    14. Sabri S,
    15. Parliament MB,
    16. Mackey J,
    17. Abdulkarim B
    : Skin toxicity in early breast cancer patients treated with field-in-field breast intensity-modulated radiotherapy versus helical inverse breast intensity-modulated radiotherapy: Results of a Phase III randomised controlled trial. Clin Oncol 33(1): 30-39, 2021. DOI: 10.1016/j.clon.2020.07.005
    OpenUrlCrossRefPubMed
    1. Parekh A,
    2. Dholakia AD,
    3. Zabranksy DJ,
    4. Asrari F,
    5. Camp M,
    6. Habibi M,
    7. Zellars R,
    8. Wright JL
    : Predictors of radiation-induced acute skin toxicity in breast cancer at a single institution: Role of fractionation and treatment volume. Adv Radiat Oncol 3(1): 8-15, 2017. DOI: 10.1016/j.adro.2017.10.007
    OpenUrlCrossRef
  42. ↵
    1. De Santis MC,
    2. Bonfantini F,
    3. Di Salvo F,
    4. Dispinzieri M,
    5. Mantero E,
    6. Soncini F,
    7. Baili P,
    8. Sant M,
    9. Bianchi G,
    10. Maggi C,
    11. Di Cosimo S,
    12. Agresti R,
    13. Pignoli E,
    14. Valdagni R,
    15. Lozza L
    : Factors influencing acute and late toxicity in the era of adjuvant hypofractionated breast radiotherapy. Breast 29: 90-95, 2016. DOI: 10.1016/j.breast.2016.07.013
    OpenUrlCrossRef
  43. ↵
    1. Wajid S,
    2. Samad FA,
    3. Syed AS,
    4. Kazi F
    : Ki-67 and its relation with complete pathological response in patients with breast cancer. Cureus 13(7): e16788, 2021. DOI: 10.7759/cureus.16788
    OpenUrlCrossRef
    1. Jain P,
    2. Doval DC,
    3. Batra U,
    4. Goyal P,
    5. Bothra SJ,
    6. Agarwal C,
    7. Choudhary DK,
    8. Yadav A,
    9. Koyalla VPB,
    10. Sharma M,
    11. Dash P,
    12. Talwar V
    : Ki-67 labeling index as a predictor of response to neoadjuvant chemotherapy in breast cancer. Jpn J Clin Oncol 49(4): 329-338, 2019. DOI: 10.1093/jjco/hyz012
    OpenUrlCrossRef
    1. Tao M,
    2. Chen S,
    3. Zhang X,
    4. Zhou Q
    : Ki-67 labeling index is a predictive marker for a pathological complete response to neoadjuvant chemotherapy in breast cancer: A meta-analysis. Medicine (Baltimore) 96(51): e9384, 2017. DOI: 10.1097/MD.0000000000009384
    OpenUrlCrossRef
  46. ↵
    1. Ishibashi N,
    2. Maebayashi T,
    3. Aizawa T,
    4. Sakaguchi M,
    5. Nishimaki H,
    6. Masuda S
    : Correlation between the Ki-67 proliferation index and response to radiation therapy in small cell lung cancer. Radiat Oncol 12(1): 16, 2017. DOI: 10.1186/s13014-016-0744-1
    OpenUrlCrossRef
  47. ↵
    1. Liu L,
    2. Yang Y,
    3. Guo Q,
    4. Ren B,
    5. Peng Q,
    6. Zou L,
    7. Zhu Y,
    8. Tian Y
    : Comparing hypofractionated to conventional fractionated radiotherapy in postmastectomy breast cancer: a meta-analysis and systematic review. Radiat Oncol 15(1): 17, 2020. DOI: 10.1186/s13014-020-1463-1
    OpenUrlCrossRefPubMed
  48. ↵
    1. Pérez-Dórame R,
    2. Mejía M,
    3. Mateos-Toledo H,
    4. Rojas-Serrano J
    : Rheumatoid arthritis-associated interstitial lung disease: Lung inflammation evaluated with high resolution computed tomography scan is correlated to rheumatoid arthritis disease activity. Reumatol Clin 11(1): 12-16, 2015. DOI: 10.1016/j.reuma.2014.02.007
    OpenUrlCrossRefPubMed
  49. ↵
    1. Shaw M,
    2. Collins BF,
    3. Ho LA,
    4. Raghu G
    : Rheumatoid arthritis-associated lung disease. Eur Respir Rev 24(135): 1-16, 2015. DOI: 10.1183/09059180.00008014
    OpenUrlFREE Full Text
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Radiation Dermatitis and Pneumonitis in Patients Irradiated for Breast Cancer
MARIE C. EGGERT, NATHAN Y. YU, DIRK RADES
In Vivo Nov 2023, 37 (6) 2654-2661; DOI: 10.21873/invivo.13374
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