Reported the results of a large retrospective review which identified oropharyngeal tumors that could be spared by contralateral ENI
Two hundred twenty-eight (280) patients with tonsillar carcinomas were treated with ipsilateral radiotherapy at Princess Margaret Hospital
Eligible patients typically had T1 or T2 tumors (191 T1 to T2, 30 T3, 7 T4) with N0 (133 N0, 35 N1, 27 N2 to N3) disease
Radiation was typically delivered with wedged pair Cobalt beams and ipsilateral low anterior neck field delivering 50 Gy in 4 weeks to the primary volume
At a median follow-up of 5.7 years:
The 3-year local control rate was 77%
Regional control rate was 80%
Cause-specific survival was 76%
Contralateral neck failure occurred in 3% (8/228)
All patients with T1 lesions or N0 neck status:
Had 100% contralateral neck control
Patients with a 10% or greater risk of contralateral neck failure included those with:
T3 lesions,lesions involving the medial one-third of the hemi-soft palate, tumors invading the middle third of the ipsilateral base of tongue, and patients with N1 disease
In the presence of ipsilateral node metastases:
The risk for contralateral neck failure was 9.5%, 14%, and 21% (all crude rates) for involvement of the soft palate, the base of tongue, and both structures, respectively
However, the authors appropriately note the limitations of these observations as they included patients with uncontrolled primaries and involved a total of only eight patients with contralateral neck failures
Despite this, the report provides confidence in the selection of patients with T1 N0 tonsil carcinomas (as well as selected patients with more advanced disease) for only ipsilateral ENI
Similar observations were also reported by Jackson et al. further supporting these observations
Given the significant risk for occult nodal involvement in certain sites of the head and neck region:
The standard of care has evolved to electively treat such patients:
Despite the lack of confirmatory randomized trials
Nodal coverage of levels I to III for oral cavity tumors and levels II to IV for oropharyngeal, hypopharyngeal, and laryngeal tumors:
Are mandatory as elective treatment
Guidelines for Neck Treatment in Patients with Head and Neck Squamous Cell Carcinomas: Echelons of Lymph Nodes to Be Treated
Elective nodal irradiation including the retropharyngeal lymph nodes is added for primary tumors involving the:
Nasopharynx, tonsil, pharyngeal wall, and the soft palate
Bilateral ENI should be considered for:
Tumors arising from or extending to midline structures such as the soft palate, the base of tongue, and the pharyngeal wall
Tumor sites such as the hypopharynx and the supraglottic larynx:
Require bilateral ENIregardless of the specific tumor stage given high risk for contralateral nodal involvement
In contrast, tumor involvement of ipsilateral structures such as the parotid, the buccal mucosa, and selected tonsil cancers warrants consideration of ipsilateral ENI
Elective nodal irradiation including level IV lymph nodes:
Should be considered in those with tumors involving the tip of the oral tongue:
Due direct drainage to this area that bypass the orderly contiguous progression in the anterior jugular nodes
Involvement of the ipsilateral level V lymph nodes in node-negative oral cavity tumors is rare:
Occurring in less than 1% of the cases , and does not warrant ENI:
However, with increasing involvement of levels I to III or the involvement of level IV, the risk for level V involvement increases warranting ENI
In contrast, involvement of only the true vocal cords does not warrant ENI due to the paucity of lymphatic drainage
Is radiation delivered locally to the resected part of the breast in the setting of lumpectomy
The benefits of APBI include:
Reduced treatment time and the potential to spare radiation to healthy tissue
Evidence to date suggests that survival and local recurrence with APBI is as effective as whole-breast irradiation:
However, careful patient selection is key
Patients suitable for APBI include:
Those ≥ 50 years old
Negative margins (by at least 2mm)
Tis or T1 tumors
Ductal carcinoma in situ (DCIS):
Screen detected
Low to intermediate nuclear grade
≤ 2.5cm
Margins of resection ≥ 3mm
APBI is considered cautionary in:
Patients 40 to 49 years old if all other criteria for suitability are met
Margins < 2mm
DCIS ≤ 3 cm and patients ≥ 50 years if patient has no unsuitable factors and at least 1 of these factors:
Size 2.1 to 3.0cm, T2 tumors, margins <2 mm, limited / focal lymph-vascular space invasion, ER– tumors, clinically unifocal tumors between 2.1-3.0 cm, invasive lobular histology, pure DCIS ≤3cm if criteria for suitability not fully met and EIC ≤3cm.
Patients are deemed unsuitable:
If they are below age 40
Between the ages of 40 to 49 years and do not meet the criteria for cautionary
Positive margins
> 3cm of DCIS
Current ASTRO guidelines do not recommend low energy IORT off prospective study, and electron IORT only for those patients with suitable risk factors
References
Correa C, Harris EE, Leonardi MC, et al. Accelerated partial breast irradiation: executive summary for the update of an ASTRO evidence-based consensus statement. Pract RadiatOncol. 2017;7(2):73-79.
Smith BD, Arthur DW, Buchholz TA, et al. Accelerated partial breast irradiation consensus statement from the American Society for Radiation Oncology (ASTRO). Int J Radiat Oncol Biol Phys. 2009;74(4):987-1001.
The efficacy of elective nodal irradiation (ENI) versus elective neck dissection:
Showed no obvious differences:
As reported by Barkley in a major retrospective experience of neck management in 596 patients with oropharynx, larynx, or hypopharynx carcinoma treated at MD Anderson Cancer Center:
Two hundred thirteen were oropharynx, 202 larynx, and 181 hypopharynx
Of these, 226 were N0 whereas 370 were node positive
Patients underwent radiation therapy (n = 292), surgical management (n = 199), or combined modality therapy (n = 105) of the neck
All patients had a minimum follow-up of 2 years and a median follow-up of 4 years
Among the electively treated patients:
Regional control was greater than 90% regardless of the treatment approach as long as comprehensive neck treatment was implemented
However, partial treatment of the neck resulted in 15%, 35%, and 20% regional failure after radiation, surgery, or combined therapy, respectively
Proton therapy for accelerated partial breast irradiation:
Remains investigational in the treatment of breast cancer
An initial phase 1 / 2 trial evaluating protons for partial breast irradiation:
Found high rates of acute skin toxicity, including:
79% moderate to severe skin color changes
22% moderate / severe desquamation
Nevertheless, physicians and patients alike reported satisfaction with cosmesis
A subsequent phase II trial involving 50 patients had minimal treatment related toxicity and excellent local control at 4-year follow-up, and post-treatment complications were thought to be less than those with more invasive techniques
References
Bush DA, Slater JD, Garberoglio C, Do S, Lum S, Slater JM. Partial breast irradiation delivered with proton beam: results of a phase II trial. Clin Breast Cancer. 2011;11(4):241-245.
Kozak KR, Smith BL, Adams J, et al. Accelerated partial-breast irradiation using proton beams: initial clinical experience. Int J Radiat Oncol Biol Phys. 2006;66(3):691-698.
Verma V, Mishra MV, Mehta MP. A systematic review of the cost and cost-effectiveness studies of proton radiotherapy. Cancer. 2016;122(10):1483-1501.
Preservation of all four parathyroid glands during total thyroidectomy is a critically important operative goal:
But this objective is not always attainable due to the extent of thyroid disease
Plus variations in the anatomical locations and blood supply of the parathyroid glands
Avoiding parathyroid damage:
First requires that the surgeon is able to recognize parathyroid tissue accurately:
The parathyroid glands are difficult to distinguish from other cervical tissues because of their small sizeand similar coloration compared to thyroid, fat, and lymph nodes
The time-honored key to parathyroid identification:
Has been a proactive anticipatory visual approach and use of surgical landmarks
Recent promise for improved parathyroid identification has arisen through:
The intraoperative stimulation of parathyroid tissue fluorescence in the presence of a contrast agent or photosensitizer (indocyanine green, amino levulinic acid hydrochloride [5-ALA], methylene blue)
Intraoperative detection with near-infrared fluorescence imaging
More recent still has been the successful detection of label-free parathyroid autofluorescence with near-infrared fluorescence spectroscopy
A gentle capsular dissection:
That reflects the perithyroidal fatty tissues off the surface of the thyroid allows for preservation of the parathyroid blood supply
This technique requires:
Dissection immediately on the surface of the thyroid gland:
Medial or anterior to the parathyroids (Figure)
Plane of capsular dissection (dotted line) during thyroidectomy, dividing vasculature medial (distal) to the parathyroid glands in order to allow preservation of the parathyroid blood supply
The importance of staying as distal to the parathyroid gland(s) as possible when dissecting cannot be overstated
Utilization of loupe magnification (2.5 X):
Has been found to significantly reduce the rate of:
Inadvertent parathyroid gland removal:
3.8% vs. 7.8%
Postoperative biochemical hypocalcemia:
20.6% vs. 33.9%; p = 0.028
Postoperative clinical hypocalcemia:
12.7% vs. 33%; p < 0.001
The use of energy devices for vessel sealing during thyroidectomy is another relevant surgical technical factor:
These energy devices generate a zone of collateral thermal spread within the tissues:
Necessitate an optimal 3 to 5 mm distance of separation between the instrument and the parathyroid gland in order to avoid thermal injury
Interestingly, it is not essential to visualize all four parathyroid glands during thyroidectomy to reduce the incidence of postoperative hypocalcemia:
Sheahan et al:
Reported that patients with zero to two parathyroid glands identified during thyroidectomy had a significantly lower incidence of clinical hypocalcemia compared to patients who had three to four parathyroid glands visualized:
3.2% vs. 17.1%; p = 0.02
In this study, the observed differences in biochemical hypocalcemia were not significant (16.1% vs. 28.1%; p = 0.13), and the incidence of inadvertent parathyroidectomywas similar (9.7% vs. 9.4%; p=1.0)
Thomusch et al:
Demonstrated that during thyroidectomy, at least two parathyroid glands should be identified and preserved in order to avoid permanent hypoPT
The inferior parathyroid glands embryologically develop along with the thymus:
And as such may be separated enough from the inferior pole of the thyroid to make their visual identification without dissection more difficult yet their preservation more likely during thyroidectomy
Thyroid cancer surgery has an increased risk of hypoPT when a central lymph node dissection is performed:
The superior parathyroid glands are at lower risk of injury or inadvertent removal than the inferior parathyroid glands:
Since most of the central neck lymph node metastases are generally located in the more inferior paratracheal and pretracheal areas
Sometimes, a small inferior parathyroid vein:
May be seen to course lateral and anterior to the carotid artery:
When identified, it is important to preserve this vein:
Which can also be followed to facilitate identification of the inferior parathyroid gland
The blood supply to an ectopic intrathymic parathyroid gland is more difficult to preserve
Central neck lymph node dissection that is ipsilateral to the primary thyroid cancer should usually be performed first:
Then, the risk of contralateral central neck lymph node metastasis must be weighed against the risk of hypoPT when deciding whether to proceed with further nodal dissection
Parathyroid autotransplantation (PA):
The identified parathyroid glands should be assessed for devascularization, and a decision made whether to perform PA:
In order to maximize the amount of retained functional parathyroid tissue
Venous congestion:
May be alleviated by sharp scoring of the parathyroid gland capsule:
Which may result in prompt normalization or improvement in color
Ischemia (arterial insufficiency) of a parathyroid gland:
May be subtle and difficult to detect, as the gland may appear only slightly pale to normal in color
A common surgical dilemma is whether autotransplantation of persistently or progressively discolored parathyroid glands is appropriate:
Promberger et al. found that patients with discolored parathyroids only had transiently impaired function:
They recommended PA:
Only if there was clear evidence of ischemia or an inadequate blood supply
PA is accomplished by:
First storing the excised parathyroid in iced saline while a sliver of the parathyroid tissue is submitted for frozen section confirmation
The parathyroid gland is then minced into 1 mm fragments that are autotransplanted by direct implantation or injection into either intramuscular or subcutaneous pockets, within the sternocleidomastoid muscle or elsewhere
The aim of PA is to reduce the risk of permanent hypoPT
Of note, much of the literature reporting on PA is focused on glands from patients with underlying hyperparathyroidism, and their observations may not extrapolate to the transplantation of devascularized parathyroids when preoperative parathyroid function was normal
Lo and Lam reported a higher incidence of postoperative hypocalcemia in patients who underwent PA during thyroidectomy compared to those who did not (21.4% vs. 8.1%; p < 0.01), but permanent hypoPT only occurred in the patients who did not undergo PA (1.8%):
However, in a different study, the same investigators found that routine PA was associated with a higher incidence of postoperative hypocalce- mia, and did not lead to a significant reduction in the incidence of permanent hypoPT when compared to a policy of selective PA
A large Australian study examined the clinical outcomes after autotransplantation of zero, one, two, or three parathyroid glands:
As the number of autotransplanted parathyroid glands increased, the incidence of temporary hypoPT increased respectively ( p < 0.05), but the incidence of permanent hypoPT was similar at less than 1% ( p = NS), respectively
Is the most common complication of bilateral and re-operative thyroid operations
The true incidence of postoperative hypoPT is debatable:
Because of significant heterogeneity in how it has been studied:
Different time points after surgery, diverse electrolyte supplementation protocols, thyroid operations of variable aggressiveness, by surgeons of varying expertise, and for a broad array of indications are further confounded by variable use of clinical criteria (symptomatic vs, asymptomatic hypocalcemia), biochemical criteria (serum parathyroid hormone [PTH] and / or calcium and / or ionized calcium), and treatment criteria (requirement for calcium and / or vitamin D supplementation)
According to a recent meta-analysis:
The median incidence of temporary hypoPT following thyroidectomy ranges from:
19% to 38%
The median incidence of permanent hypoPT following thyroidectomy ranges from:
0% to 3%
It is critically important for the thyroid surgeon to employ strategies for minimizing and preventing hypoPT, including:
Carrying out the most appropriate extent of thyroidectomy for a specific patient
Background:
The short half-life of PTH (3 to 5 minutes), along with the fragile nature of the parathyroid glands:
Sets the stage for their functional derangement following manipulation
The etiology of hypoPT:
Is related to dissection or removal of the vulnerable parathyroid glands during central neck operations:
Resulting in a decline in circulating PTH
Definitions
Biochemical hypoPT:
Is defined as a low intact PTH level:
Below the lower limit of the laboratory standard (usually 12 pg/mL):
Ranges of normal PTH values vary:
Depending upon the laboratory
Accompanied by hypocalcemia:
Hypocalcemia is a total serum calcium level that is less than the lower limit of the center-specific reference range
Transient serum calcium values outside the normal reference range:
May reflect dynamic changes in electrolytes and state of hydration:
Rather than true hypocalcemia
Hypocalcemia may occur independent of hypoPT, but untreated hypoPT always leads to hypocalcemia, even though time lag can range from hours to days.
Clinical hypoPT:
Is defined as biochemical hypoPT that is accompanied by symptoms and/or signs of hypocalcemia
Parathyroid insufficiency, or relative hypoPT:
May occur after central neck surgery
Typically is manifested by clinical symptoms of hypoPT that require medical treatment:
Despite measured laboratory values within normal ranges
Transient or temporary hypoPT:
Is defined as occurring for less than six months after surgery:
Permanent hypoPT:
Is defined as occurring beyond six months after surgery
Mechanisms:
The mechanisms that underlie hypoPT:
Are related to:
Disruption of parathyroid gland arterial supply
Disruption of parathyroid gland venous drainage
Mechanical injury
Thermal or electrical injury
Intentional or inadvertent partial or complete removal
Normal parathyroid function requires a rich blood supply:
A normal parathyroid gland is composed of up to 30% capillary cells
Parathyroid blood supply is both delicate and complex:
Requires close attention during thyroidectomy to ensure its preservation
While the inferior thyroid artery is typically the dominant blood vessel that supplies the parathyroid glands:
Laser Doppler flowmetry has shown that:
The superior thyroid artery and vessels within the thymo-thyroid cord (ligament) can dominate in some individuals
Impaired PTH secretion results in postoperative hypocalcemia through:
Inhibition of bone resorption
Reduction of 1,25-dihyroxyvitamin D synthesis by the kidneys
Reduced intestinal absorption of calcium
Symptoms and signs:
Hypocalcemia causes:
Neuromuscular excitability and cardiac electrical instability:
Due to a reduced nerve and muscle cell depolarization threshold
Its most common early symptoms are:
Paresthesias, or numbness and tingling, of the perioral region and the fingertips
Muscle stiffness, cramps, and spasms are also common
Neuropsychiatric symptoms include:
Confusion, anger, depression, lightheadedness, and irritability
More sustained muscle contraction may lead to:
Laryngospasm
More severe neural excitability:
May lead to seizures
Signs of hypocalcemia include:
Observed or elicited tetany:
Classic bedside findings are:
A positive Chvostek sign:
Facial muscle twitching upon tapping the preauricular region over the facial nerve:
Present at baseline in up to 25% of people
A positive Trousseau sign:
Flexion of the wrist, thumb, and metacarpophalangeal joints and hyperextension of the fingers, upon brachial artery occlusion by inflation of a blood pressure cuff above systolic blood pressure)
Cardiovascular signs observed with progressive hypocalcemia include:
Prolongation of the QT interval that can result in torsades de pointes:
A form of ventricular tachycardia that may degenerate into ventricular fibrillation.
Risk factors:
HypoPT may follow any simultaneous or staged bilateral central neck operation
Risk factors for both temporary and permanent hypoPT are presented in the following Table:
A prior partial thyroid operation creates a potentially increased risk of hypoPT during completion thyroidectomy:
Due to unknown status (presence or viability) of the parathyroid glands in the previously operated neck
The most straightforward way to avoid hypoPT:
Is to limit the extent of thyroidectomy to a unilateral approach
Though the historical rationale for a near-total or subtotal thyroidectomy
Instead of a total thyroidectomy, is in part preservation of the parathyroid glands:
It has never been adequately studied whether this actually reduces the risk of hypoPT
Parathyroid autotransplantation (PA):
At the time of thyroidectomy has been associated with an increased risk of temporary hypoPT
Paradoxically, routine PA may be associated with a reduced risk of permanent hypoPT
While data supporting propyhylactic PA are not definitive:
The risk of permanent hypoPT is very low in patients who have undergone autotransplantation of at least one parathyroid gland
Preoperative vitamin d deficiency:
When the planned thyroid operation is bilateral:
Preoperative testing of baseline serum calcium, PTH, and 25-hydroxy vitamin D blood levels can be helpful
If the baseline calcium is low normal, or below normal:
The risk of hypoPT is increased:
It may be appropriate to initiate scheduled oral calcium supplementation preoperatively
If the baseline calcium level is elevated:
Then the PTH level should be measured in order to evaluate for occult primary hyperparathyroidism, which could be definitively treated during thyroidectomy
A preoperatively elevated PTH level is commonly due to secondary hyperparathyroidism from vitamin D deficiency:
Vitamin D increases the absorption of calcium from the intestinal tract, and supplementation may be helpful to patients with hypoPT:
Assuming no underlying malabsorptive condition is present
Vitamin D also increases bone resorption and decreases renal excretion of calcium and phosphate
Vitamin D deficiency can be:
Severe – below the lowest recordable level, less than 10 ng/mL
Moderate – 10 to less than 20 ng/ mL
Mild (20 to 30 ng/mL
To optimize postoperative oral calcium absorption:
It is prudent to treat vitamin D deficiency preoperatively:
The Food and Drug Administration (FDA) approved regimen is:
50,000 IU of vitamin D3 (cholecalciferol) weekly or 6000 IU daily for eight weeks
More aggressive regimens and other vitamin D supplements are available, but their utilization should be considered off-label
Not all studies have substantiated improved postoperative calcium levels with higher preoperative vitamin D levels:
Lang et al. found the rate of clinically significant hypocalcemia after total thyroidectomy to be similar in patients with severe, moderate, and mild vitamin D deficiency, whereas Al-Khatib et al. found that severe 25-hydroxyvitamin D deficiency was an independent predictor of hypoPT in patients undergoing total thyroidectomy:
However, a large meta-analysis reported that the perioperative PTH level, the preoperative vitamin D level, and postoperative changes of calcium were biochemical predictors of post-thyroidectomy hypocalcemia
Given the present evidence, it would appear preferable to diagnose vitamin D deficiency and initiate appropriate corrective supplementation prior to surgery
In cases of elective bilateral thyroid surgery:
It may be prudent to delay surgery in order to correct severe vitamin D deficiency
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Was a randomized controlled trial comparing completion axillary lymph node dissection (ALND) versus axillary radiotherapy (ART):
In women with clinical T1 to T2, N0 who were found to have a positive sentinel lymph node upon undergoing sentinel lymph node biopsy
Axillary RT was to levels I to III and SCV fossa:
To 50 Gy / 25 fractions
The primary endpoint was:
Non-inferiority of 5-year axillary recurrence
The 5-year axillary lymph node recurrence rate:
As 0.43% in the ALND group and 1.19% in the ART group (p=non-significant), with authors concluding that ALND and ART offer excellent and comparable axillary control in this set of patients
Of note, non-randomized patients with a negative sentinel lymph node biopsy had a similar axillary recurrence rate of 0.8%
Disease-free and overall survival were similar between the two arms
Lymphedema:
Was increased in those receiving ALND (23% vs. 11%, p<0.001 with clinical signs; 13% vs. 5%, p=0.0009 with arm circumference > 10%)
This result echoes findings of the ACOSOG Z0011 trial with low rates of axillary recurrence while omitting ALND
Those offering their expert opinion have agreed that results from these two randomized trials support the omission of ALND in patients with a clinically node negative axilla and a low burden of node positive disease found upon sentinel lymph node dissection
References
Donker M, Van Teinhoven G, Straver M, et al. Radiotherapy or surgery of the axilla after a positive sentinel node in breast cancer (EORTC 10981-22023 AMAROS): a randomised, multicentre, open-label, phase 3 non-inferiority trial. Lancet Oncol. 2014;15(12):1303-1310.
Giuliano AE, McCall L, Beitsch P, et al. Locoregional recurrence after sentinel lymph node dissection with or without axillary dissection in patients with sentinel lymph node metastases: the American College of Surgeons Oncology Group Z0011 randomized trial. Ann Surg. 2010;252(3):426-432.
Mahmoud O, Haffty B. Regional nodal management in the light of the AMAROS trial. Ann Transl Med. 2015; 3(7):88.
Is extremely rare and is seen in less than 1% of patients who receive radiotherapy for breast cancer
Polgár et al:
Found an incidence of 0.46 per 1,000 cases at their institution
Radiation-induced angiosarcoma:
Was associated with a latency period of 6 to 8 years in that study
Additional studies have demonstrated an interval of 3 to 12 years:
With a median time to development of 6 years
Presentation often includes:
A bruise-like appearance in the treated region:
So a high index of suspicion is needed to make the diagnosis
Treatment includes:
Surgery with or without radiation:
But radiation is not contraindicated
Smith et al. treated patients with hyperfractionated accelerated re-irradiation therapy with or without surgery:
Utilizing three radiation therapy treatments each day:
With a minimum interfraction interval of 4 hours, 5 days a week:
At 1 Gy per fraction, to total doses of 45 Gy, 60 Gy, and 75 Gy for areas with a moderate risk for subclinical disease, a high risk for subclinical disease, and gross disease, respectively
Toxicity was minimal
Median survival was 7 years:
10-year cause specific was 71%
These numbers are better than the 5-year overall survival of 40% and local control rates of approximately 30% reported by Depla et al
References
Abbott R, Palmieri C. Angiosarcoma of the breast following surgery and radiotherapy for breast cancer. Nat Clin Pract Oncol. 2008;5(12):727-736.
Polgár C, Orosz Z, Szerdahelyi A, et al. Postirradiation angiosarcoma of the chest wall and breast: issues of radiogenic origin, diagnosis, and treatment in two cases. Oncology. 2001;60(1):31-34.
Smith TL, Morris CG, Mendenhall NP. Angiosarcoma after breast-conserving therapy: long-term disease control and late effects with hyperfractionated accelerated re-irradiation (HART). Acta Oncol. 2014;53(2):235-241.
Koerner F. Sarcoma. In: Hoda S, Brogi E, Koerner F, Rosen PP, eds. Rosen’s Breast Pathology. 4th ed. Philadelphia, PA: LWW, Wolters Klumer; 2014:1118–1126.
Depla AL, Scharloo-Kareis CH, de Jong MA, et al. Treatment and prognostic factors of radiation- associated angiosarcoma (RAAS) after primary breast cancer: a systematic review. Eur J Cancer. 2014;50(1):1779-1788.
Tri-modality therapy for patients with breast cancer can result in complications
In women undergoing adjuvant radiation therapy, treatment of the regional nodes:
Is associated with higher rates of lymphedema
The published MA-20 trial:
Found an 8.4% rate of lymphedema with regional nodal irradiation compared with 4.5% without
As a part of the toxicity discussion a patient has with her provider, it is worth noting that there is no strong evidence of worse lymphedema:
When comprehensive post mastectomy RT is delivered using hypofractionation versus conventional fractionation:
Analysis of the START trials found no difference in shoulder stiffness (11% standard fractionation vs.14% hypofractionation), difficulty raising arm (17% standard fractionation vs. 14% hypofractionation), lymphedema (11% standard fractionation vs. 6% hypofractionation)
Shoulder dysfunction:
Can also be seen in patients requiring regional nodal irradiation:
With data documenting significant differences in shoulder function in patients with a history of breast cancer
Breast edema:
Can be noted acutely during radiotherapy as well as chronically following treatment:
With toxicity rates of 5%
There is evidence supporting an increased risk of ischemic heart disease in the years following breast radiotherapy:
Albeit with some criticism as these conclusions were largely based on antiquated radiation techniques
No data suggest an increased risk of pulmonary embolus with radiation for breast cancer
References
Shah C, Vicini FA. Breast cancer-related arm lymphedema: incidence rates, diagnostic technique, optimal management, and risk reduction strategies. Int J Radiat Oncol Biol Phys. 2011;81(4):907-914.
Whelan TJ, Olivotto IA, Pareulekar WR, et al. Regional nodal irradiation in early-stage breast cancer. N Engl J Med. 2015;373(4):307-316.
Haviland JS, Manino M, Griffin C, et al. Late normal tissue effects in the arm and shoulder following lymphatic radiotherapy: results from the UK START (Standardisation of Breast Radiotherapy) trials. Radiother Oncol. 2018;126(1):155-162.
Harrington S, Padua D, Battaglini C, et al. Comparison of shoulder flexibility, strength, and function between breast cancer survivors and healthy participants. J Cancer Surviv. 2011;5(2):167-174.
Hille-Betz U, Baske B, Bremer M, et al. Late radiation side effects, cosmetic outcomes, and pain in breast cancer patients after breast-conserving surgery and three-dimensional conformal radiotherapy: risk modifying factors. Strahlenther Onkol. 2016;192(1):8-16.
Darby SC, Ewertz M, McGale P. Risk of ischemic heart disease in women after radiotherapy for breast cancer. New Engl J Med. 2013;368(11):987-998.
Rodrigo Arrangoiz MS, MD, FACS, FSSO 