Beam quality
HVL (mm Al)
Soft
0.020–0.022
Medium
0.023–0.029
Hard
0.030–0.036
D½—The D ½ philosophy which is discussed elsewhere in this treatise requires that the chosen beam penetrates and is not attenuated more than 50 % to the base of the tumor or condition.
Beam quality | D ½ (mm) |
|---|---|
Soft | ~0.5 |
Hard | ~ 1.0 |
Wavelength—Bucky and others have defined grenz ray by their wavelength which ranges from 1 to 4 Ǻ. The correlation between tube kV and wavelength has been described by the formula:
Wavelength (min) = 12.354/kV
Other Physical Properties
In the grenz ray region, backscatter is not significant and absorption curves are essentially equivalent to depth dose curves. The depth dose increases very slowly between soft and medium and more so between medium and hard. Above 0.036 mm Al HVL the depth dose and quality as one gets into the region of superficial radiation escalates much quicker [1]. For this reason, Bucky set the upper limit of grenz ray at 0.036 mm Al HVL. In deference to him, the Council for the Study of Grenz Ray Therapy set the upper limit of the grenz ray range at HVL 0.035 mm Al on March 17, 1950 [2].
Calibration
Most radiation physicists are not familiar with or equipped to calibrate a grenz ray unit. Many therapy physicists do not possess the thin window chamber and thin aluminum sheets required for the calibration of these units. Chambers with Mylar windows work well and one example is the Capintec PS-033. This chamber has an ultrathin Mylar 0.5 mg/cm2 window. Not all Accredited Dosimetry Calibration Laboratories (ADCLs) can calibrate these chambers at grenz ray kVs; however, at the time of the printing of this text, K&S Associates of Nashville, Tennessee provides this service. Dermatologists employing grenz ray should employ a physicist experienced with this modality. Although the present protocol by the American Association of Physicists in Medicine (AAPM) for X-ray therapy calibration Report 76 by Task Group #61 does not address X-ray therapy below 40 kV X-ray beams, it can be used as a general guide to the calibration of grenz ray machines. The British Journal of Radiology supplement 25 is another good source of information, because it contains percent depth dose and backscatter information for beams with HVLs as thin as 0.01 mm Al. It has been the experience of the authors that our grenz ray unit, which is infrequently used, takes more time, effort, and cost to calibrate than our standard 50/70/100 kV unit or our backup 80 kV unit.
The cone’s circumference is generally limited to ¾ of the TSD. There is a significant drop off at the shoulder of the field, due to the fact that because of air absorption, the TSD is significantly longer at the perimeter than that of the central beam. Hollander, in his classic 1952 treatise on grenz ray [2], relates that the measured beam reduction when one goes from a TSD of 10–20 cm is 78 % of that calculated by the inverse square law. This falls to a 44 % reduction of the calculated beam when one goes from a TSD of 10–50 cm. This drop-off diminishes to 88 % of the calculated beam from a TSD of 10–20 cm with a 20 kV beam. Accurate calibration is vital and far more complex with grenz ray than any other modality. This is in order to reduce the chance of under or over treatment of in situ malignancies or inflammatory disease, both of which can have serious consequences and constitute mistreatment.
We recently contacted our physicist to help us produce a beam which had a D ½ of 1 mm. We needed to treat atypical junctional melanocytic proliferation in elderly patients with equivocal slow Mohs margins or be able to recreate the Miescher technique as a primary therapy for elderly or feeble patients with facial lentigo maligna. This process required the HVL of the unit to be increased from 0.038 to 0.06 mm Al. This was accomplished by adding a 0.08 mm Al filter to the beam. The consequence of using this filter is a drastic reduction in dose output.
Radiobiological Effect of Grenz Ray
In his classic 1928 book, Gustav Bucky states that “the employment of electromagnetic oscillations from about 2 Ǻ units produces unique clinical and biological manifestations” [3].
Grenz ray photons are absorbed mainly by the photoelectric effect. The resulting photoelectrons have a short path, because their energy is equal to that of the initiating photon minus the binding energy of the electron shell. Previous studies have shown that when looking at the range from 3 to1000 kV, the coefficient of chromosome breakage peaks at 4.1 Ǻ [4]. Comparative studies of the biologic effect of X-rays and neutrons to other ionizing radiation have been performed. The low energy photons of grenz ray are comparable to higher energy gamma rays based on the dominance of photoelectric absorption at low energies. The relative biologic effectiveness (RBE) increases as the energy of photons and the energy of the secondary electrons emitted decreases. This translates into an increase in linear energy transfer (LET) or stopping power, with a D max at the skin surface (as with all photon radiotherapy) where the majority of energy is absorbed within the epidermis and upper dermis.
Several studies have shown a marked and sustained reduction in Langerhan cells at 1 and 3 weeks [5–9]. The deposition of the majority of its modest energy in the epidermis, and its effect on Langerhan cells may explain why grenz ray has been used successfully for inflammatory disease such as contact dermatitis, eczema, and psoriasis and in situ/superficial/precancerous neoplasms including lentigo maligna, squamous cell carcinoma in situ (SCCIS), superficial basal cell carcinoma (sBCC), and actinic keratosis [10].
Physical Effects of Grenz Ray
Early on, grenz ray dosages and therapeutic treatment were prescribed in increments and multiples of the clinically observed and measured erythema dose. This was similar to ultraviolet therapy. The erythema dose of grenz ray appears earlier and can be more intense than that of superficial radiotherapy and has been measured at between 250 and 400 cGy. At higher single or cumulative dosages, this erythema can be quite intense and is not a contraindication for continued or further treatments. In fact, in its extreme (i.e., the Miescher technique), one expects and strives for a brisk desquamative response which occurs between a cumulative dose of 3,000–10,000 cGy over a 1–2 week period, in fractions of 1,000–2,000 cGy. Clinicians look for and carefully document the erythema seen after one or two 200–300 cGy treatment fractions as evidence and clinical assurance that the tube is functioning well and is well-calibrated.
Cosmesis
Pigmentation often occurs and can be longstanding. This can be especially significant and disconcerting when treating lentigo maligna, where the pigmentation may persist and take 6–12 months to resolve. Pigmentation is accentuated when lead shields are used because the line of demarcation is sharp. However, pigmentation is diffuse when open cones are used and the central field fades into the peripheral field. This is because of the difference in the TSD centrally vs. peripherally. Epilation has been reported to rarely occur. Hollander calculated that to achieve a reversible epilating dose of 350 cGy to the hair bulb, one must give a 5,000 cGy surface dose of grenz ray with a HVL of 0 0.034 mm Al where 7 % reaches the bulb. Long-term sequellae such as telangiectasias and atrophy have been described by early workers in the field and in clinicians who did not take care to protect themselves or their patients from chronic cumulative large doses. Secondary basal cell carcinomas (BCCs) and squamous cell carcinomas (SCCs) have been reported at doses over 100 Gy (vide infra).
Grenz Ray for In Situ Malignancies and Precancers
Grenz Ray for Lentigo Maligna
In the Miescher technique, a beryllium-window tube at 12 kV was used with an additional 1 mm thick filter of tissue-equivalent material (Cellon). 10,000 cGy in 5 fractions of 2,000 cGy were given every 3–4 days [11]. In 1971 Kopf et al. reported on the use of the Miescher technique in eight patients with lentigo maligna, using 12 kV and a D ½ of 1.3 mm [12]. In 1976 they published follow up data on the original eight patients, as well as eight subsequent patients treated in the interim between 1971 and 1976 [13]. Of these original 16 patients, five had recurrences or residual disease and three developed metastatic disease. This brought an abrupt end to the use of grenz ray in their department, and had a dampening effect on the use of grenz ray for lentigo maligna in the United States. One postulated downfall in the original study by Kopf et al. had been that patients who developed metastases had probably progressed to LMM with dermal invasion prior to treatment with the Miescher technique.
Despite this honest display of failure, others before and after have utilized grenz ray, superficial X-ray, and even electrons for lentigo maligna. Desquamative dosage/fractionation plans have been used in patients who were poor surgical candidates or had diffuse/non-resectable disease.
The D ½ philosophy for the treatment of malignancies suggests that radiation quality for a given lesion should deliver at least 50 % of the surface dose to the deepest part of the tumor. Under this concept, most in situ neoplasms can be treated with grenz ray using a D ½ between 0.5 and 1 mm.
In a retrospective study, Farshad et al. included 150 patients with lentigo maligna (LM) and lentigo maligna melanoma (LMM). Ninety-three had LM, 54 had LMM, and 3 had both (Farshad et al. calculated that 96 had LM and 57 had LMM). They employed the use of grenz ray (12 kV, 100–120 Gy at 3–4 day intervals for 10–12 fractions with a D ½ of 1 mm) in 96 patients with LM and 11 with LMM. Fifty-seven patients also received deeper penetrating X-rays (20 or 30 kV). Forty-six patients with LMM received 42–54 Gy (20–50 kV) at 3–4 day intervals over 7–9 fractions. There was a 7 % recurrence rate in 101 of 150 patients available for 2-year follow up [14]. They recommended using a safety margin around the visible lesion of at least 10 mm, in order to prevent recurrences at the edge of the radiotherapy field.
In another study, Schmid-Wendtner et al. excised the nodular portions of LMM before irradiation of the lentiginous part of the lesion [15]. They found that once LM transitions into LMM, superficial X-ray is less effective than in LM. They treated 64 patients (42 had LM and 22 had LMM) with a total dose of 100 Gy applied in 10 fractions (5 fractions per week over 2 weeks at 14.5 kV, D ½ of 1.1 mm). No patients with LM had recurrence, but 2 of 22 patients with LMM needed surgical excision for local recurrence.
Over a 30-year period, physicians at the Princess Margaret Hospital in Ontario, Canada treated patients with orthovoltage radiotherapy for LM and LMM. The following three studies highlight their experience. They give reference to the Miescher technique despite the fact that all three studies utilized deeper penetrating X-rays.
In the first of the three studies, Dancuart et al. looked at the fact that only one third of all histologically proven LMM show nodule formation clinically [16]. In their study they avoided the Miescher technique because of the difficulty in determining dermal extension. Using this as a reference point, they utilized conventional orthovoltage radiotherapy to treat eight patients with LM and 15 patients with LMM. Their patients were treated with either 100 kV (HVL 0.7 mm Al), 140 kV (HVL 3.6 mm Al), or 280 kV (HVL 1.25 or 3 mm Cu). The authors felt that they avoided “geographic miss” of dermal extension in LM and LMM by using a minimum irradiation energy of 100 kV with a D ½ of 6 mm. 1 of the 8 patients with LM had a recurrence on the edge of the previously treated irradiated zone 12 months after initial irradiation. The patient was treated with further radiation and did well. 6 of the 8 patients with LM achieved remission for 1–4½ years following radiotherapy. 1 of the 8 patients with LM had residual pigmentation on the cheek. 14 of the 15 patients treated from LMM went into remission. Two of those 14 had some residual pigmentation. 1 of the 15 patients with LMM had a central recurrence, but was treated with salvage excision and did well. In general, doses ranged between 3,500 cGy in 5 fractions and 4,500–5,000 cGy in 10–15 fractions.
In the second of the three studies that utilized orthovoltage radiotherapy, Harwood published similarly successful results using 100 kV (HVL 0.7 mm Al) for LM (23 patients) and 125–175 kV for LMM (28 patients) [17]. Patients were treated with 3,500 cGy for 5 fractions in 1 week, 4,500 cGy for 10 fractions in 2 weeks, or 5,000 cGy for 15–20 fractions in 3–4 weeks. 18 of 23 patients with LM had no recurrence. Two patients with LM failed irradiation. 1 of those 2 patients refused conventional irradiation and was treated with a single exposure of 2,000 cGy, but the lesion persisted and was excised. The second patient had an edge recurrence and was doing well after he was re-irradiated. The final three patients could not be evaluated because of short follow-up time. 23 of 28 patients with LMM were locally controlled for 6 months to 8 years. Two of 28 patients with LMM developed local recurrence treated with salvage excision. 3 of the 28 patients were not assessable because of short follow-up time. 1 of those 3 had a level five LMM that arose in a preexisting LM. Harwood noted that lesions may take up to 2 years to completely regress following treatment.
Although surgical excision remains the treatment of choice for small lesions of LM, in the last of the three studies, Tsang et al. demonstrated that orthovoltage radiotherapy was a good alternative for large lesions in facial areas. They demonstrated that radiotherapy was also a cost-effective treatment strategy, on par with excisional surgery. They looked at 54 patients with LM. There were 18 younger patients treated with excision, and 36 older patients with larger lesions treated with radiotherapy. 1 of the 18 younger patients had a recurrence treated with salvage excision. 3 of the 36 older patients’ disease not controlled by irradiation alone were successfully treated with salvage excision. The excision revealed invasive melanoma in 2 of the 3 patients (no papules or nodules present clinically). One patient with residual pigmentation was unavailable for follow up [18].
Gaspar et al. pointed out the fact that the major drawback with radiotherapy treatment of LM is the lack of histopathologic confirmation that there is no LMM present. They looked at treatments for LM. After reviewing many of the studies done, they concluded that radiotherapy is an acceptable treatment for LM if used by experienced clinicians [19].
A recent well-done study from Sweden published by Hedblad et al., looked at grenz ray treatment of LM and early LMM over almost 20 years. Five hundred and ninety-three patients were treated with grenz rays in three groups [20]. The grenz ray unit delivered a HVL of 0.02 mm Al with a D ½ of 0.5 mm. Treatment doses ranged from 100 to 160 Gy twice weekly over 3 weeks. Grenz ray was curative in 520 of 593 patients (88 %) overall in all three groups, after one fractionated treatment. Complete clearance was seen in 290 of 350 patients (83 %) in the group receiving primary treatment with grenz ray alone. The complete clearance rate in the group of patients who received partial excision followed by grenz ray was 64 of 71 (90 %). Lastly, the complete clearance rate in the group of patients who received prophylactic grenz ray after radical excision was 166 of 172 (97 %).
Hedblad et al. reported that 73 of 593 patients (12 %) did not clear in one fractionated treatment. Within the group that did not clear in one fractionated treatment, 15 of 73 (21 %) had a weak radiation dermatitis with residual lesions, and 36 of 73 patients (49 %) had recurrence. Skin folds and residual “field effects” contributed to the recurrences due to the application of insufficient safety margins. The remaining 22 of 73 patients who did not clear in one fractionated treatment (30 %) showed histological changes consistent with proliferation of atypical melanocytes in adnexal structures.
Hedblad et al. treated 46 of 73 (63 %) patients who had recurrent or persistent lesions with additional fractionated grenz ray treatment. Three additional grenz ray treatments were combined with shave excision, and eight additional grenz ray treatments were combined with surgical excision. Several teaching points were highlighted by the authors. The first lesson was that high risk relapse sites are often seen in areas with hyperplastic adnexal structures such as the ala nasi, beard area, and scalp. In order to reduce recurrences, they recommended distending deep skin folds and wrinkles near the forehead and eyes when the cone is applied. In addition, the authors encouraged the use of a Woods light to help demarcate the clinical borders of the lesion so that sufficient safety margins of at least 1 cm can be used.
Grenz Ray for Bowen’s Disease
There are a variety of treatment options for Bowen’s disease or SCCIS depending on the histological characteristics of the lesion. As with LM and LMM, surgical removal offers the highest cure rate, but there are topical chemotherapeutic drugs, photodynamic therapy, and local destructive modalities that can successfully treat this tumor. In addition, various X-ray treatments have been used against SCCIS.
In 1977, Stevens et al. published a report of 19 lesions of SCCIS treated 2–3 times a week using 12–14 kV and 500 cGy over 10 fractions for a total dose of 5,000 Gy [21]. The HVL was 0.030–0.034 mm Al, and the D ½ was 0.7–0.9 mm. Of the 19 lesions treated, 17 had good cosmesis with successful treatment. One lesion persisted and was found to be superficially invasive SCC after excision. One lesion recurred 4 months after grenz ray treatment was completed. The depth of the overlying scale combined with the depth of the lesion exceeded the D ½, explaining why treatment with grenz ray failed.
Renato G. Panizzon, former editor of this book and a renowned expert on grenz ray and photon radiation therapy, recommended a dosage of 6 Gy twice weekly for 12 fractions using a D ½ of 1 mm [22]. In the event that there is significant adnexal involvement, then superficial radiotherapy or orthovoltage may be a better choice of treatment.
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