Brachytherapy: Applications and Technique, 1st Edition

6. Thoracic Brachytherapy

 

Subhakar Mutyala

David J. Sugarbaker

Esophageal Cancer

There will be an estimated 15,000 patients with esophageal cancers in the United States in 2006. In the United States, the incidence of adenocarcinoma of the esophagus is increasing, whereas that of squamous cell carcinoma is decreasing slightly. Worldwide, the incidence of squamous cell carcinoma is much higher than in the United States. This being said, the US death rate in 2006 will be an estimated 13,000. Despite the accessibility of the organ, only 6% of esophageal cancers receive brachytherapy, according to the Patterns of Care Study.1

Brachytherapy as Boost for Definitive Radiation

Procedure

The recommended applicator is a single channel catheter, with a diameter of 0.6 to 1.0 cm. A thinner catheter would lead to a higher mucosal dose, and therefore, higher toxicity. A picture of a commercially available catheter from Nucletron Co. (Veenendal, Netherlands) can be seen in Figure 6.1.

The procedure should be conducted in an appropriate operating room or procedure suite. The patient should be anesthetized with moderate sedation and local anesthesia or general anesthesia. Often the catheter can be inserted transnasally after nasal dilation and anesthesia. However, in the setting of a high-grade obstruction, a more complicated approach is indicated. As before, the goal is to have the esophageal applicator placed through the nose. If the patient has a gastrostomy tube, the procedure can be done quite easily. The applicator can be passed through the nose and led out of the mouth. Then the endoscope is passed through the mouth and advanced, until the gastrostomy tube is visualized. A long suture or snare should be inserted into the gastrostomy tube and grasped by the endoscope. The endoscope should be withdrawn, pulling the suture out through the patient's mouth, while care must be taken to have the other end of the suture secure outside the gastrostomy tube. The suture (or snare) should be attached to the weighted end of the esophageal catheter and slowly pulled from the gastrostomy tube while advancing the catheter into the patient's mouth. If the endoscope cannot pass the obstruction, an additional step of passing a thin biopsy catheter past the lesion may work, thereby grabbing the snare, which, in turn, will be used to draw the applicator safely down. Care must be taken so as not to disrupt the mucosa or to create a false lumen. These procedures require a high level of endoscopic skill and carry significant potential risk of bleeding, mediastinitis, infection and belong in tertiary referral centers with significant caseloads.

 

Figure 6.1 A high dose rate esophageal catheter from Nucletron Co. (Veenendal, Netherlands). The catheter is much thicker than an endobronchial catheter to spare the mucosa from a high dose of radiation.

Once the catheter has traversed the obstruction, the endoscope should be reintroduced to visually confirm the position of the catheter. The catheter should be stabilized and secured to the patient's nose with some temporary fixative, such as benzoin and silk tape. An x-ray or computed tomography (CT) scan should be taken for treatment planning with metal dummies in place through the central channel. Typically, the prescribed dose is 1 cm from the channel. With CT scan–guided treatment planning, dose optimization can be done to achieve a more custom dose, at a depth of 5 mm into mucosa. Figure 6.2 demonstrates an esophageal catheter successfully placed in a patient.

Dose

The American Brachytherapy Society (ABS) published its consensus guidelines for the use of brachytherapy for a boost, after external beam radiation therapy (EBRT).2 The use should be limited to thoracic disease, short in length, and localized disease to the esophagus. The selection criteria can be seen in Table 6.1. Brachytherapy could be used after external beam, usually 45 to 50 Gy in 1.8 to 2.0 Gy per fraction, typically waiting 2 to 3 weeks. The dose could be delivered with high dose rate (HDR) (10 Gy, at 5 Gy fraction size, weekly) or low dose rate (LDR) (20 Gy, in a single course, at 0.4 to 1.0 Gy per hour) with dose prescribed at 1 cm from the source position. The recommended dose schema can be seen in Table 6.2.

The ABS recommendations for palliation can be seen in Table 6.3. Typically, the dose is delivered in 5 to 10 Gy fraction size. External beam should be added and brachytherapy decreased for patients with longer life expectancy, to decrease the long-term side effects.

Experience

High Dose Rate for Boost

There are two randomized series comparing EBRT with and without brachytherapy. The first from China3 had 200 patients. The dose delivered by external beam radiation alone was 70 Gy in 35 fractions compared with 50 Gy external beam in 25 fractions plus 3 to 4 applications of middle dose rate (MDR) brachytherapy for a dose of 19.6 to 26.16 Gy.
The 5-year local control was improved in the brachytherapy arm, 61.3% versus 43% and 5-year overall survival was also improved 17% versus 10% (p<0.05). The toxicity was reported to be the same, 12.6% of perforation or hemorrhage in either arm. The second randomized study from India4 had similar results for 50 patients. The dose prescribed was 55 Gy EBRT versus 35 Gy EBRT and 12 Gy HDR boost in 2 fractions 1 week apart. The complication rate was higher strictures in the brachytherapy arm, 8% versus 4%.

Figure 6.2 An esophageal catheter in place with metal dummies to simulate dwell positions. The treatment area is outlined by the physician.

Table 6.1 American Brachytherapy Society Selection Criteria for Brachytherapy in the Treatment of Esophageal Cancer

Good candidates
   Primary tumor ≤10 cm in length
   Tumor confined to esophageal wall
   Thoracic esophagus location
   No regional lymph node or systemic metastasis
Poor candidates
   Extraesophageal extension
   Tumor >10 cm in length
   Regional lymphadenopathy
   Tumor involving gastroesophageal junction or cardia
Contraindications
   Esophageal fistula
   Cervical esophageal location
   Stenosis which cannot be bypassed

Adapted from Gaspar LE, Nag S, Herskovic A, et al. American Brachytherapy Society (ABS) consensus guidelines for brachytherapy of esophageal cancer. Clinical Research Committee, American Brachytherapy Society, Philadelphia, PA. Int J Radiat Oncol Biol Phys. 1997;38(1):127–132.

 

Table 6.2 American Brachytherapy Society Suggested Schema for Definitive External Beam Radiation and Esophageal Brachytherapy

External beam radiation
   45–50 Gy in 1.8–2.0 Gy/fraction, 5 fractions/wk, wk 1–5
Brachytherapy
   High dose rate—total dose of 10 Gy, 5 Gy/fraction, 1 fraction/wk, starting 2–3 wk following completion of external beam
   Low dose rate—total dose of 20 Gy, single course, 0.4–1.0 Gy/hr, starting 2–3 wk following completion of external beam

All doses specified at 1.0 cm from mid-source or mid-dwell position.

With chemoradiation becoming the standard of care5 of nonsurgical definitive treatment for esophageal cancer, the addition of brachytherapy needed to be investigated. Radiation Therapy Oncology Group (RTOG) opened a phase I/II study (RTOG 92 to 07) to compare cis-diamminedichloroplatinum (CDDP) and 5-fluorouracil (5-FU), with 50 Gy EBRT, followed by three 5 Gy HDR fractions. The catheter used was 0.4 to 0.6 cm in diameter and the dose was prescribed to 1 cm from the channel. After 70% of the patients were added, a large perforation rate was noted: 58% grade 3, 26% grade 4, and 8% grade 5 (fatal). The dose was lowered to 5 Gy HDR fractions × 2 for the remaining patients. Neither of these remaining patients had a grade 4 or 5 toxicity. The local control was 37%. On the basis of the low local control and high toxicity, the study did not progress to phase III.

Table 6.3 The American Brachytherapy Society Consensus Guidelines for Esophageal Brachytherapy for Palliation

Recurrent after external beam radiation or short life expectancy
   Brachytherapy
      High dose rate—total dose of 10–14 Gy, 1 or 2 fractions
      Low dose rate—total dose of 20–40 Gy, 1 or 2 fractions, 0.4–1.0 Gy/hr
No previous external beam radiation
   External beam radiation
      30–40 Gy in 2–3 Gy fractions
   Brachytherapy
      High dose rate—total dose of 10–14 Gy, 1 or 2 fractions
      Low dose rate—total dose of 20–25 Gy, single course, 0.4–1.0 Gy/hr
No previous external beam radiation, life expectancy >6 mo
   External beam radiation
      45–50 Gy in 1.8–2.0 Gy/fraction, 5 fractions/wk, wk 1–5
   Brachytherapy
      High dose rate—total dose of 10 Gy, 5 Gy/fraction, 1 fraction/wk, starting 2–3 wk
      following completion of external beam
      Low dose rate—total dose of 20 Gy, single course, 0.4–1.0 Gy/hr, starting 2–3 wk
      following completion of external beam

The RTOG study6 used more chemotherapy, smaller catheters, and higher doses of brachytherapy. This could explain the weaker mucosa and higher perforation rates. Several subsequent phase II studies7,8,9 show higher local control and lower toxicity. Calais added Mitomycin-C with CDDP and 5-FU to 60 Gy EBRT and two 5 Gy fractions. The 3-year local control was 57% with 11% long-term toxicity. Iwasa showed improved local control and survival with three 6 Gy fractions of HDR. Table 6.4 shows the toxicity and fraction schema of several studies.

The best role for the addition of brachytherapy for esophageal cancer would be in stage I tumors. Superficial tumors, described as being only mucosal or submucosal, have shown responses and low toxicity.16,17,18 This area might be controversial as The Japanese Society for Therapeutic Radiation Oncology released a contradictory study that for superficial lesions, brachytherapy had no benefit over EBRT;19 however, most studies show a benefit with low toxicity, especially for the mucosal lesions.

Brachytherapy for Palliation

Several series have reported using brachytherapy alone for palliation. Jager20 reports using 15 Gy in a single fraction at 1 cm from the channel. There was a reported 67% improvement of dysphagia with only 6% stricture. Sur21 reported increased number of fractions (three 6 Gy fractions compared with two 8 Gy fractions), improved dysphagia—38.9% relief compared with 25.4% but increased stricture and fistula rate. Sharma22 reported reasonable toxicity rates, 15% stricture, 10% ulcer, and 5% fistula formation for two 6 Gy fractions. There was a higher incidence of toxicity from patients who received radiation previously—38% versus 27%.

Newer therapies have been compared or added to brachytherapy. Two randomized studies compared stenting with brachytherapy.23,24 Both studies showed stenting to cause quick resolution of dysphagia, but, eventually, the results were the same. Brachytherapy, however, resulted in less pain, less need for further procedures, and better quality of life. Emerging techniques combine laser with brachytherapy25 or radioactive stents.26

Table 6.4 Table of Toxicity for Esophageal Endoluminal Brachytherapy

Author

N

External Beam Radiation Therapy/Fxs

Brachytherapy

Stricture %

Ulcer %

Fistula %

Yin3

64

50 Gy/25

20–26

NR

6

6

 

64

70 Gy/35

0

NR

5

5

Hishikawa10

148

60 Gy/30

12

15

55

4

Flores11

145

40 Gy/15

15

35

NR

5

Immerzeal12

54

50 Gy

15

NR

7

<5

 

46

60 Gy

12

NR

25

<5

Gava13

132

60 Gy/30

13–20.8

18

7.5

4

Kumar14

42

54.5 Gy

8–10

2.4

NR

2.4

 

11

51 Gy

10–12

9

NR

0

 

22

49 Gy

12–15

36

NR

14

Gaspar6

39

50 Gy/25

15

NR

NR

12

 

10

50 Gy/25

10

NR

NR

0

Churn8

32

45–55 Gy

20–22(low dose rate)
8.5–10 (high dose rate)

19

19

6

Sharma15

50

50 Gy/28

20

24

 

1302

 

50

50 Gy/28

15

8

28

12

N, number of patients; Fxs, number of fractions; NR, not reported.

Lung Cancer

Lung cancer will have approximately 170,000 new cases per year in the United States. It remains the number one cancer in incidence and the number one cause of cancer deaths. Lung cancer has had a long history with brachytherapy, from Yankauer inserting Ra-226 into lung cancer in 192227 and Graham and Singer placing Radon 222 needles into lung tumors in1933.28 Currently, brachytherapy is used widely for lung cancer and for several stages. Following are the uses of interstitial brachytherapy for early stage and locally advanced lung cancer, interoperative radiation, and brachytherapy for endobronchial lesions and palliation.

Early Stage Disease

Surgery for early stage lung cancer is the gold standard definitive treatment. The recommended surgery has always been lobectomy or pneumonectomy. The Lung Cancer Study Group showed that sublobar resection had decreased local control.29 A large resection requires the patient to have a reasonable FEV1 (0.8 to 1.2 L) and a ventilation-perfusion scan corresponding to adequate breathing in other segments. Patients who have long histories of smoking commonly fail to have this lung reserve to handle a large resection. A new technique is to perform smaller surgery with radioactive seeds at the margin. There are several reports of wedge resection for Stage I tumors with placement of the 125I seed at the resection margin. This can be done to perform surgery on patients who cannot undergo a lobectomy or pneumonectomy or who are at a higher risk stage I.

Planar Seed Implant Technique

After a wedge or sublobar resection, the length and width of the area at risk should be measured. These will be the dimensions of the implant. The implant is composed of 125I in Vicryl suture, called Seed-in-Carrier, with ten seeds at 1-cm distance. These sources are commercially available from Oncura Corp (Plymouth Meeting, PA). Each seed is 0.7 mm by 4 mm. After the “at-risk” area is measured out, a custom cutout of an absorbable suture (either Daxon or Vicryl) in mesh form is made. Usually, another centimeter of mesh in all dimensions is needed to suture the implant in place. The area should be drawn with parallel lines drawn longitudinally with 0.7- to 1.5-cm spacing (see Figures 6.3, 6.4, 6.5, 6.6, 6.7 and 6.8). The exact spacing between the sutures of the seed should be based on the activity of the seeds being implanted. Nomograms from the University of Pittsburgh (see Figure 6.9) and Memorial Sloan-Kettering Cancer Center (MSKCC) (see Figure 6.10) help assist the physician to prospectively plan the dosimetry on the basis of the implant size and the activity of the seeds. The sources should be stitched into the mesh following the lines drawn, remembering that the suture should only be handled with forceps. The suture should be anchored on either side with a small staple and any excess sources on the suture should be cut and disposed of properly, according to radiation protection guidelines. The custom mesh should be placed in the at-risk area and sutured into place, with care taken to not puncture a seed. After the operation is over and patient is stable (can be a future date), a CT scan should be taken through the area, with dosimetric planning to follow. This will verify and document the dose that the patient will receive.

Planar Implant Experience

The largest published series comes from Allegheny General Hospital.30 A retrospective series of 101 patients with sublobar resection and seeds placed at the suture line were compared with 102 similar patients with sublobar resection alone. Patients were surgically resected using the video-assisted thoracic surgery (VATS) approach. The implants were made on Vicryl mesh and planned with a dose of 100 to 120 Gy at 0.5-cm distance from the plane.


The mesh was then sutured to the staple line. The local relapse rates are 2% for seeds (at 18 months) versus 18.6% for sublobar resection alone (at 24 months) (p = 0.0001). Age and FEV1 were similar in both groups, but the group with the implants had more stage IB patients (23) than the surgery alone group (0). Overall, the 4-year survival was 60% and 67% for surgery alone and surgery plus implant, not statistically significant. Published data of longer follow-up31,32,33 confirm the long-term disease-free and overall survival of these patients.

Figure 6.3 Under sterile technique, the suture seed carrier is stitched into the absorbable mesh along grid lines drawn to control the distance between the strands. Note the careful use of long instruments. This implant is 15 × 9 cm (160 seeds) to cover a target area of 13 × 7 cm with 1-cm margin. Ten seeds will cover 9 cm.

Figure 6.4 The completed implant can be trimmed to match the operative bed.

 

Figure 6.5 A smaller implant 9 × 6 cm (70 seeds) to cover a 7 × 4 target area with 1-cm margin. The sutures are passed through the mesh at least four times per strand and secured with small surgical clips.

Figure 6.6 The suture strand is pulled through a mesh along the grid line. Clips are applied at each end to secure the strands in mesh.

 

Figure 6.7 An even smaller implant (40 seeds) 7 × 4.5 cm to cover a target area of 5 × 3 cm can be made by doubling back to the next grid line with the same strand. Once the seeds are removed from the steel shield, the implant can be placed in a steel basin at the back of the table to minimize the radiation exposure to the operating room staff.

Figure 6.8 The last implant being sewn in with absorbable sutures over the target area previously agreed upon and measured out by the surgeon and the brachytherapist.

 

Figure 6.9 Nomogram from the University of Pittsburgh for permanent planar 125I seed dosimetry.

New England Medical Center and Tufts University has another series34 of 33 patients who underwent a wedge resection (or segmental resection) and implant. The technique varied slightly, with implanting the strands of seed directly on the suture line, without mesh. The dose intended was 125 to 140 Gy at 1-cm depth. The results show 2/33 (6%) recurrence at the suture line (median follow-up 51 months) with a 5-year projected survival of 47%. The cancer-specific 5-year survival was 61%.

A new technique on the horizon shows the implanting of the seeds robotically. Pisch35 describes the resection of small tumors with a wedge resection and implantation of the 125I seeds using the Da Vinci Robot, to assist in fine movements and distances in the chest. Reports are early, but the procedure appears to be feasible with longer follow-up necessary.

Implanting Tumor

If the patient cannot undergo surgery, the tumor itself could be implanted. Although this technique has much inferior results compared with surgery, for patients who cannot undergo any surgical resection, this might be the only option to increase dose. The tumor and any gross disease should be implanted with radioactive seed, usually Iodine 125. A needle must be inserted into the tumor and then seeds dropped, either individually or in a line. This technique is called a volume implant. The seeds must be placed to cover a volume of disease, as opposed to the prior technique, a planar implant. MSKCC described this technique36 with 65% locoregional control. A more recent study from the Norris Cancer Center37 describes volume implants on 14 patients. All patients had lymphatics surgically staged. Iodine 125 was used to implant the tumor. There was a 71% local control rate with 15 months' median follow-up. All the relapses were in patients who had a stage III tumor.
The dose delivered was 80 Gy at the periphery with a high dose of 200 Gy in the center of the tumor. There was no incidence of radiation pneumonitis.

Figure 6.10 Lowell Anderson Nomogram from Memorial Sloan-Kettering Cancer Center for 125I permanent implants seed dosimetry.

Locally Advanced Disease

Surgical Limitations

Certain tumors are deemed unresectable or marginally resectable on the basis of anatomic locations, such as proximity to bones or great vessels. Brachytherapy can assist in converting an unresectable, or marginally resectable, tumor into an acceptable oncologic resection. After maximal resection by the surgeon, the area at risk (close or positive margin) must be noted by the radiation oncologist and surgeon. The area should be measured, usually adding 0.5–1 cm to all dimensions for a radiation dosimetric margin. The geometry of the implant could take any shape; however, a rectangle is the easiest to make and to perform dosimetry on. One way to clear this margin is to place a permanent planar implant with interstitial seeds. The description on how to fashion an implant and how to place it is given in the preceding text. Toxicity from this type of implant is low38, with 7.9% grade 3 to 4 toxicity defined as requiring surgical intervention. The specific toxicities were hydropneumothorax, radiation pneumonitis, and esophageal fistulas. The esophageal fistulas39 were from placing the implant on an esophagus which had been surgically violated, and the muscular layer was not of full thickness. The dosimetry of a planar seed implant for a superior sulcus tumor is pictured in Figure 6.11.

Figure 6.11 Dosimetry of a planar seed implant for a superior sulcus tumor.

Planar Seed Placement

Retrospective series from MSKCC40 showed that stage III patients with mediastinal involvement had similar median survival (16 vs. 17 months) and 5-year survival (15%) for complete resection versus incomplete resection plus brachytherapy, which were both better than no resection and brachytherapy alone or no resection and no brachytherapy. In another series with all lung cancer stages, had an increase of 50% medial survival (8 to 12 months) with brachytherapy after incomplete resection compared with no surgery.41 This was compared with 17-month median survival for complete resection.

New York Hospital42 looked at this technique in a prospective study. Twelve patients with stage III non–small cell lung cancer (NSCLC) who had gross or microscopically positive margins after resection were implanted with a planar implant. The implants were composed of either 125I or 103Pd embedded in a Gelfoam plaque. The dose prescribed was to a 1-cm margin around the area of positive margin. All patients received either preoperative or postoperative external beam, from 45 to 60 Gy. The results showed 82% local control with the addition of brachytherapy for positive margin after surgery. The 2-year overall and cancer-specific survivals were 45% and 56% respectively. MSKCC43, in another series, also reported a 75% locoregional control with partial resection and implant, compared with an 86% locoregional control with full resection.

Intraoperative Radiation Therapy and Afterloading Catheters

Another therapy was to treat a close and positive margin with IORT. This can be delivered in two methods, with afterloading or IORT. Afterloading involved placing hollow blind-ended plastic catheters along the area at risk, with the radioactive sources inserted into the catheters “after” the surgery. The catheters should be spaced out by 1 cm in parallel lines. The open end of the catheter should be directed out of the skin. Care must be taken to not kink the catheters in any sharp angles, as this would not allow after loading. After appropriate time is given for the patient to stabilize, the patient should have a computer-generated treatment plan in the radiation department.

Afterloading

Afterloading can be treated with two techniques, LDR or HDR. LDR requires the patient to have active radioactive sources on a string to be placed into the catheters and to remain for a few days. During the interim, the patient must be isolated in a radiation safe room, with full radiation precautions. The radiation and catheters are removed at the appropriate time and the patient can be removed from radiation precautions. HDR could be done with an afterloader, such as Nucletron Co. (Veenendal, Netherlands) microSelectron or a similar device. The patient is implanted with the same catheters as mentioned in the preceding text. The radiation is delivered with only one source, which is computer controlled and can be placed at various positions and dwell times. This flexibility allows for more dose conformality than LDR. Also, all treatment is delivered in a shielded room, eliminating the dose to staff. Both techniques are considered radiobiologically equivalent. MSKCC44 reported implanting the mediastinum with afterloading techniques (LDR) with good local control and 2-year actuarial survival (76% and 51% respectively) for N2 disease. Another group from Seattle45 also showed good local control with the addition of brachytherapy.

Intraoperative Radiation Therapy

For IORT, more equipment is needed. The radiation can be delivered using a mobile accelerator into a shielded operating room or in the radiation department, where a radiation vault is also a functional operating room. The area at risk must be demarcated by the surgeon. The normal tissue can be moved out of the field or shielded with thin strips of lead. Either the cone from the linear accelerator is inserted into the patient or an applicator for HDR brachytherapy is placed, such as the HAM applicator (Mick Industries, Bronx NY). All personnel must leave the room before the radiation is delivered, which usually lasts only a few minutes.

Intraoperative Radiation Therapy Experience

Several series have been published, describing this technique. The largest series in the literature is from University Clinic of Navarra, Pamplona, Spain.46 They retrospectively reported 104 patients from 1984 to 1993, stages IIIA and IIIB. From 1984 to 1989, 22 patients had surgery, IORT, followed by EBRT, and from 1989 to 1993, 82 patients had neoadjuvant chemotherapy. Responders (46 patients) had surgery, IORT, and EBRT; nonresponders had chemoradiation, surgery, with IORT as a final boost. Their technique used 10 to 15 Gy (18 to 20 Gy unresectable). The series reported that local control rates for patients with microscopic residual disease was 66% (33/50) and for patients with macroscopic residual, 35% (15/42). The best results were seen in Pancoast tumors, which had local control of 92% (11/12) and 100% (5/5) for microscopic and macroscopic diseases, respectively. The most common toxic event was grade III–IV esophagitis in 25%. Other reported toxicities were symptomatic pneumonitis, transient neuropathy, and lung fibrosis.

Complications

Complications from any of these techniques are similar and minimal compared with the surgery itself. There could be some instance of poor wound healing or abscess formation, although very rare. The most concerning toxicity would be fistula formation. Care must be used to not place the seeds directly on any injured organ, such as esophagus39 or blood vessels. Intact tissue can tolerate the very low dose rate (VLDR) radiation well; however, any injury, either by tumor or surgery, can predispose to a fistula. This can be avoided if implant is necessary by adding another layer of luminal protection for the vessel of esophagus, by biologic or artificial technique.

Mesothelioma

High dose rate intraoperative radiation therapy (HDRIORT) was performed under protocol at MSKCC for the intraoperative management of locally aggressive thoracic mesothelioma. The long-term outcome of this therapy was marred by postoperative complications, and the practice has been discontinued. There are anecdotal experiences with permanent VLDR implants for recurrent thoracic mesothelioma when margins are positive or unsure and when additional postoperative EBRT cannot be given.

Recurrence or Metastasis

Tumor recurrence or metastasis can be treated with brachytherapy. Brachytherapy has an advantage, as it can be used in patients for tumors which have already received radiation.


Care must be taken in re-irradiating the heart, spinal cord, or esophagus; the other organs can tolerate re-irradiation with brachytherapy well. Depending on the location and surgical resection, any technique could be used—permanent seeds, afterloading catheters, or IORT. Sometimes seeds would be preferred owing to the slower rate of radiation. The slower the rate of radiation, the more can be given for re-irradiation. LDR and VLDR may be better tolerated by normal tissue compared with HDR on certain risky organs. For a description of the techniques, see the preceding text.

Endobronchial Lesions

Endobronchial Primary

Some early data is present with uses of endobronchial therapy for boost in addition to external beam therapy for definitive treatment. One pilot study47showed good results for small superficial lesions limited to the bronchus. The treatment dose was 5 fractions of 7 Gy at 1.0-cm depth. The 2-year actuarial survival was 58%, but with 2/19 deaths from late toxicity (hemoptysis). Although, theoretically, the dose could be escalated with endobronchial therapy, no data shows that this prolongs the survival or increases local control. Another phase II study48 shows that the addition of endobronchial radiation decreases the symptoms without any change in the overall survival.

Palliation

One of the most common uses of brachytherapy is endobronchial brachytherapy for palliation. Commonly, patients with lung disease can get obstructive pneumonia, hemoptysis, or both. These symptoms can drastically affect the quality of life or can even be life threatening. Radiation can be administered for palliation, either with external beam or with brachytherapy. Brachytherapy provides a benefit as higher doses could be directly given to the tumor, sparing normal lung. The main disadvantage of brachytherapy would be subjecting the patient to a procedure to insert the catheter, which some end-stage patients may not be able to tolerate. The ABS recommends a selection process for patients to receive brachytherapy as shown in Table 6.5.

Procedure

The patient should be placed under anesthesia, either moderate sedation or general anesthesia. If under general, the patient should be orally intubated. The nasal cavity should be dilated, with cocaine or Afrin, to reduce nasal swelling. The bronchoscope should be introduced in the nose and advanced around the ET tube into the airway to visualize the lesion. After the tumor is visualized, a brachytherapy catheter should be threaded through the operating side port of the bronchoscope. An example of a commercially available catheter from Nucletron Co. (Veenendal, Netherlands) is pictured in Figure 6.12. The proximal end should remain outside of the bronchoscope and the distal end should be visualized to be distal to the tumor, by at least 2 cm. The bronchoscope is slowly removed over the catheter, with care being taken to keep the catheter at its position in the bronchus. The bronchoscope should be reintroduced, finally through the ET tube to confirm the catheter's place and to ensure that there is no kinking. A kinked catheter will not allow therapy and must be replaced before leaving the OR. The catheter should be secured to the nose with a fixative, such as benzoin and silk tape. The proximal and distal extent of the tumor in relation to the catheter should be noted for treatment planning, usually under fluoroscopy.

Table 6.5 American Brachytherapy Society's Recommendations for Endobronchial Brachytherapy

Patients with significant endobronchial tumor component, causing symptoms such as shortness of breath, hemoptysis, persistent cough, and signs of postobstructive pneumonitis. Tumors that protrude into the lumen are considered suitable, as opposed to extrinsic tumors that compress the bronchus or the trachea. The catheter should be able to pass into (and preferably past) the obstructed bronchus. Endobronchial brachytherapy can generally give a quicker palliation of obstruction than EBRT. Furthermore, brachytherapy can be more convenient compared with 2 to 3 wk of daily EBRT for many patients.
Patients who do not undergo resection because of poor lung function or distant metastasis.
Patients who, because of poor lung function, are unable to tolerate any external irradiation.
Patients with previous EBRT of sufficient total dose to preclude further EBRT.
Patients with sufficient life expectancy (usually >3 mo) to benefit from palliation.

EBRT, external beam radiation therapy.

Figure 6.12 An endobronchial high dose rate catheter—6F, 150 cm.

Either an x-ray or a CT scan should be taken for treatment planning, with radiopaque source markers (dummies). The treatment should be planned, with the prescription point typically 1 cm from the catheter, unless the treatment is optimized with three-dimensional images. An example of an x-ray with catheter and dummies in place is pictured in Figure 6.13. LDR dose recommendations from the ABS are 30 Gy at 1.0 cm from the catheter channel.49 HDR recommendations are four 6 Gy fractions, three 7.5 Gy fractions, or one 10 Gy fraction at 1 cm from the catheter. The fractionation schema should be individualized to the patient, depending on the patient's stability for procedures and life expectancy (see Figures 6.14, 6.15 and 6.16).

Experience

A comparison was made between EBRT and EBRT plus endobronchial radiation.50 This was carried out in a randomized fashion with 95 patients. The endobronchial treatment was two 7.5 Gy fractions 1 week apart. The EBRT was 30 Gy in 10 fractions or 60 Gy in 30 fractions. The results showed added benefit with endobronchial therapy by increasing the incidence of re-expansion and decreasing the incidence of dyspnea, along with prolonging the duration of palliation. The toxicity was low in either arm, 13% versus 15% of massive hemoptysis.

Figure 6.13 An endobronchial high dose rate catheter in place with a radiopaque dummy strand demonstrating a good position in the right upper lobe. Note the indication of the area to treat on film.

Figure 6.14 An endobronchial high dose rate catheter is introduced through the side port of the bronchoscope.

 

Figure 6.15 Care is taken to pass the catheter 1 cm at a time so as not to kink.

Figure 6.16 An endobronchial high dose rate catheter exits the side port and can be seen in the airway ahead of the bronchoscope.

Another randomized study51 compared EBRT with endobronchial brachytherapy. The doses were 30 Gy in 10 to 12 fractions versus 1 fraction of 15 Gy at 1.0 cm by HDR. The results showed a better relief of symptoms with EBRT versus brachytherapy, 91% versus 76% respectively. There was also a modest improvement in survival, 287 versus 250 days, respectively. Also, more patients who received brachytherapy required EBRT (51%) later compared with patients who received EBRT requiring brachytherapy (28%) later. The toxicity profiles were identical.

The M.D. Anderson Cancer Center published the 10-year experience with endobronchial brachytherapy for palliation. There were 175 patients, 160 of whom had received previous EBRT. The treatment regimen was 15 Gy in 2 fractions at 6 mm from the catheter for a total of 30 Gy. Results showed 66% subjective improvement (34% slight improvement, 32% significant improvement) and 78% objective improvement on repeat bronchoscopy. The complications were 11% with massive hemoptysis at 5%. Table 6.6 is a summary of the published series on endobronchial brachytherapy.

Complications

The major complications of endobronchial brachytherapy, outside of the procedural events from bronchoscopy, are massive hemoptysis and bronchial necrosis. Hemoptysis is controversial with regard to the etiology—whether the treatment or the tumor is to blame. A basic science study57 shows the bronchial wall to be very resistant to high doses of radiation, up to 45 Gy single fraction size, with statistically different cell viability at 60 to 75 Gy single fraction size. By fractionating the treatment, both the toxicities from the treatment could be avoided. Langendijk50,58 showed that a treatment dose of 7.5 Gy or 10 Gy had 11% of deaths from hemoptysis, similar to controls; however, 15 Gy at 1 cm had almost 50% death from hemoptysis. Similar results from Italy59 state that fractionating the dose from 10 Gy × 1, 7 Gy × 2, and 5 Gy × 3 (all prescribed to 1 cm), had similar responses, but less side effects with the greater number of fractions. Some newer techniques60,61 have created centering mechanisms for catheters. This could decrease the catheter mobility and unintentional hot spots on the bronchial wall, theoretically the reason for hemoptysis and stenosis.

Table 6.6 Published Experience with Endobronchial Therapy

Institution

Patients

Dose

EBRT

Results

M.D. Anderson52

175

15 Gy at 6 mm

Yes (160)

66% subjective improvement
78% objective improvement

Hackensack University53

117

5 Gy × 3 at 1 cm

Yes, 37.5 Gy

72% resolution of symptoms
54% bronchoscopic response

Defense Military Service, Madrid54

81

5 Gy × 4 at 0.5–1 cm

No

85% symptomatic complete response
56% bronchoscopic complete response

Ankara University55

95

7.5 Gy × 3 or 10 Gy × 2 at 1 cm

Some patients with history of EBRT

All symptoms responded (details not given)

Clinique Sainte Catherine56

189

8–10 Gy × 3–4 at 1 cm

Some patients with history of EBRT (69.3%)

Responses:
Hemoptysis 74%
Dyspnea 54%
Cough 54%

EBRT, external beam radiation therapy.

 

Combination with New Techniques

Brachytherapy is now improved with the addition of new surgical advances. Allison62 reports the placement of a metallic stent, followed by brachytherapy of three fractions of 6 Gy at 0.5-cm depth. The early data shows an increase in Kornofshy performance status (KPS) in all patients and a decrease in hemoptysis. Chella63 reported a series of patients treated with Yttrium-aluminum-garnet (YAG) laser ± brachytherapy for three 5 Gy fractions at 0.5-cm depth. The follow-up showed a statistically significant increase in the duration of freedom from symptoms for the combination group, 2.8 months versus 8.5 months. Freitag64combined photodynamic therapy (PDT) with brachytherapy for bronchogenic carcinoma with good results, 100% OS at 24 months. Santos65 compared the multimodality treatment, of YAG laser, stenting, PDT, or brachytherapy with a combination of any of the treatments. The multimodality group had a statistically significant improvement in survival.

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