Patterns of breast cancer radiotherapy practices among Saudi radiation oncologists

Discussion

Breast cancer is the most common cancer among Saudi women, and the incidence rate of breast cancer continues to rise.^9,10 Radiotherapy plays a major role in the management of breast cancer. However, there are worldwide variations in the practice of radiotherapy as well as in Saudi Arabia, perhaps because of the different training backgrounds of radiation oncologists.⁷

Ductal carcinoma in situ is not a common diagnosis in Saudi Arabia; however, national efforts to raise awareness regarding the early detection of breast cancer and improvements in health care accessibility are expected to increase the rate of DCIS diagnoses. Breast conservative surgery with adjuvant radiotherapy is the standard of care for DCIS.¹¹ Although the management of DCIS closely follows that of early breast cancer, there are a few differences. The Society of Surgical Oncology, American Society for Radiation Oncology and American Society of Clinical Oncology published a joint consensus guideline on the margins for breast-conserving surgery with whole-breast irradiation in DCIS, indicating 2 mm as the minimum acceptable margin. However, clinical judgment is required to decide on the necessity and suitability of re-excision.¹² Boost radiotherapy to the surgical bed is not widely adopted for DCIS because trials on the role of boost radiotherapy largely focus on invasive cancer.⁷ Nevertheless, there is an evidence to suggest an improvement in local control with the use of tumor bed boost radiotherapy in DCIS.¹³

Hypofractionation at a dose of 40/15 or 42.5/16 is the standard of care after breast conservative surgery.¹⁴ However, the use of hypofractionation for locoregional treatment as well as in the setting of PMRT with or without immediate reconstruction is controversial.⁷ The Danish and Canadian postmastectomy landmark trials that revealed survival advantage following the addition of adjuvant radiation after mastectomy have actually delivered hypofractionated regimens..^15,16 In the United Kingdom (UK), it is standard practice to offer hypofractionated radiotherapy to all patients in the adjuvant setting.¹⁷ The Canadians are currently recruiting for a phase 3 randomized trial of standard versus hypofractionated radiotherapy after mastectomy with or without reconstruction.¹⁸ The Study of Radiation Fractionation on Patient Outcomes After Breast REConstruction (FABREC) is a phase 2 trial that is recruiting and investigating whether hypofractionated radiotherapy to the chest wall and the regional lymph nodes is superior to standard fractionation in the reconstructed breast.¹⁹ Wang et al²⁰ found hypofractionated radiotherapy to be non-inferior to standard fractionation in the setting of T3-T4 or N2 disease.

The benefits of PMRT are controversial; nevertheless, there is a strong consensus among Saudi radiation oncologists regarding using PMRT. Postmastectomy radiotherapy is indicated for advanced primary or nodal disease.¹⁶ However, the value of PMRT for N1 disease or high-risk nodal negative disease is in question, particularly in the better systemic therapy setting.^6,21 Two randomized phase 3 trials are underway to clarify the value of PMRT: the UK Selective Use of Postoperative Radiotherapy After Mastectomy (SUPREMO) trial, which is looking for the role of PMRT in high-risk node-negative patients and N disease²² and the Tailor RT trial, a Canadian trial investigating the predictive value of low-risk oncotype DX recurrence scores in N1 patients.²³ The use of a bolus with PMRT is another vague area with conflicting evidence. Some departments use a bolus for all patients, whereas others use it only in patients with skin involvement. Daily bolus on alternate days or half the bolus on consecutive days are 2 different practices.⁷ Some authors reported a higher risk of recurrence when a bolus is not used, whereas others demonstrated similar local control with the routine omission of the bolus when no skin involvement was observed.^24,25 Variations in the bolus placement practice are, therefore, expected.

The majority of postmastectomy trials as well as trials of locoregional irradiation after breast-conserving surgery included comprehensive nodal radiotherapy with the inclusion of the InM chain of lymphatics.^6,16 Nonetheless, indications for RNI and radiation volumes are still controversial. Excluding the dissected axilla (or intentionally not including it) from the radiotherapy field in the adequate axillary dissection setting, the definition of which is debatable, is clearly not a standard practice among responders. Neither is the inclusion of the InM lymph nodes, reflecting worldwide variation in practices.⁷ Radiation to the InM chain recently gained interest, particularly with the technique modifications that allow for cardiac and lung dose reduction.⁶

Treatment planning volumes and techniques vary among radiation oncologists not only nationwide, but worldwide, and is the area with the most variation among respondents in this survey, particularly concerning the InM volumes and coverage criteria. Intensity modulated radiotherapy is an acceptable practice in some centers while standard fields remain in others.⁷ Several contouring guidelines have been published.^26,27 However, standard fields do not adequately cover the recommended targets, and the decision to expand the field to cover these targets or acceptance of inadequate coverage should be cautiously individualized. In addition, InM recurrences have been reported outside the recommended contours.²⁸ There is no consensus regarding the definition of acceptable coverage for the InM lymph nodes, and careful modification of the recommended volume to ensure adequate coverage of the targets should be balanced against the potential toxicity of radiotherapy.^28-30

The DIBH technique for patients with left-sided breast cancer is widely adopted.⁷ Limitations to the routine use of DIBH techniques in certain centers are the cost and significant resource commitment required, and our study responses revealed that 25% of the respondents would not use DIBH techniques because of the lack of availability.³¹

At the time of writing this manuscript, the world had been suffering from the effects of the coronavirus disease (COVID-19) pandemic. Many radiotherapy centers around the world adopted measures to reduce patient and staff exposure to potential infections. Although some measures were not based on level one evidence, the severity of the situation has mandated bold measures. These measures included omitting radiotherapy when deemed of little or no definitive benefit in the adjuvant setting or reducing the number of fractions when deemed acceptable. For breast cancer, in particular, radiotherapy after lumpectomy for node-negative, early-stage, and hormone-positive disease can be omitted.³² Additionally, an expedited review and publication of the 5-year results of the FAST-forward trial investigating 5 daily fractions of 5.7 Gy in the adjuvant setting coincided with the emerging need for hypofractionation and was quickly adopted, at least for early disease and during the current global pandemic situation.^32,33

This study is an effort to look into the practice of radiation oncologists in Saudi Arabia. I have addressed almost all of the controversies related to breast radiotherapy. However, I acknowledge the inherent weakness of web-based surveys, such as the lack of accountability and accuracy and the association with a failure to personally explain confusing questions or answer choices. Additionally, the relatively small and underrepresented number of respondents in this survey may be overcome in the future by expanding the inclusion criteria for the study participants.

In conclusion, radiotherapy practice variations among Saudi radiation oncologists echo international variations in many aspects due to the lack of strong evidence and availability of resources. Resource allocation, particularly for DIBH techniques, and the establishment of national guidelines, are recommended to decrease the disparity in radiotherapy practice and promote the exchange of data and national research collaborations. Prospective follow-up data collection at the national level should be initiated to identify possible dissimilarities in our patient characteristics as well as the potential need for treatment intensification, particularly in areas of international variations.

Future research is required to answer the questions raised and expand the study areas to include radiation oncologists from the Gulf, Arab, and Middle Eastern countries.