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HEAD AND NECK SYMPOSIUM - ORIGINAL ARTICLE
Year : 2014  |  Volume : 51  |  Issue : 3  |  Page : 241-244
 

Modern chemoradiation practices for malignant tumors of the trachea: An institutional experience


Department of Radiotherapy and Oncology, All India Institute of Medical Sciences, New Delhi, India

Date of Web Publication10-Dec-2014

Correspondence Address:
N Joshi
Department of Radiotherapy and Oncology, All India Institute of Medical Sciences, New Delhi
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0019-509X.146743

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 » Abstract 

Background: Malignant tumors of the trachea are rare. A multimodality treatment approach is often necessary. Outcomes of radical non-surgical approaches are sparse. Radiation combined with sequential or concurrent chemotherapy is an important treatment option. Materials and Methods: We present an analysis of outcomes using modern radiotherapy and chemotherapy for tracheal tumors. Results: Radiation dose escalation using modern techniques is of benefit for these tumors. The results with chemotherapy are encouraging. Conclusions: Radiation plays a distinct role and should be a part of treatment for these tumors. The role of chemotherapy needs to be studied further.


Keywords: Chemoradiation, modern, tracheal tumors


How to cite this article:
Joshi N, Mallick S, Haresh K P, Gandhi A, Prabhakar R, Laviraj M A, Sharma D N, Julka P K, Rath G K. Modern chemoradiation practices for malignant tumors of the trachea: An institutional experience. Indian J Cancer 2014;51:241-4

How to cite this URL:
Joshi N, Mallick S, Haresh K P, Gandhi A, Prabhakar R, Laviraj M A, Sharma D N, Julka P K, Rath G K. Modern chemoradiation practices for malignant tumors of the trachea: An institutional experience. Indian J Cancer [serial online] 2014 [cited 2019 Sep 19];51:241-4. Available from: http://www.indianjcancer.com/text.asp?2014/51/3/241/146743



 » Introduction Top


Malignant tumors of the trachea are rare, accounting for only 0.1-0.4% of all cancers. [1] Prospective treatment experience is lacking. Hence, clinical data for these tumors comes from retrospective institutional series and individual case reports. These tumors are associated with considerable mortality and morbidity as they involve the major airway. Histologies involved are often aggressive. The anatomy involved makes surgery difficult. Incomplete or marginal resections are common and adjuvant treatment is paramount in all, but the rarest of cases. There also exists the possibility of definitive treatment with chemoradiation alone. Therefore, a multimodality treatment approach is needed. While epidemiology, histopathology, and survival statistics of these tumors are known, outcomes of radical non-surgical approaches are sparse. Both radiation and chemotherapy are used in the management of this disease. While radiation has become more precise, newer chemotherapy agents have also been developed. We present an institutional analysis with an aim of analyzing the outcomes of modern radiation delivery and chemotherapy for the management of tracheal malignancies.


 » Materials and Methods Top


We retrospectively analyzed our database for the last 5 years. Patients treated with both radical and palliative intent were included. Patient immobilization was achieved using a customized thermoplastic device and thoracic base plate for each patient treated with three dimensional conformal radiation therapy (3DCRT). All patients were simulated in the supine position using a Siemens 4 slice computed tomography (CT) scanner or a Phillips 4DCT Big Bore (TM) CT scanner. All patients including the Intensity modulated radiotherapy (IMRT) plan utilized coplanar beam positioning, and thus the supine position with both hands placed at the patient's side was acceptable. The datasets were imported into our planning systems, namely Eclipse (TM) for 3DCRT and Pinnacle (TM) for the IMRT plan.

Radiation therapy volumes were defined as follows: Gross tumor volume (GTV) included all gross visible disease on imaging and endoscopy. The GTV was expanded 2 cm craniocaudally, and 1 cm circumferentially to generate a clinical target volume (CTV). The planning target volume (PTV) was created by adding a uniform 3-10 mm expansion to the CTV. For 3DCRT plans without image guidance, a 10-mm expansion was used. For the IMRT plan, a 4DCT scan was done. Maximal intensity projection algorithm was used to generate an image accounting for internal motion. This was fused with free breathing CT images. The GTV and CTV were created as above, resulting in an internal target volume (ITV). The PTV was then created by giving a 3-mm margin on the ITV. The doses for each plan were prescribed to the appropriate isodoses, with the objective of achieving adequate volume coverage while maintaining dose homogeneity. 3DCRT setup verification was done using digitally reconstructed radiographs, with a conventional simulator CT. The IMRT plan execution included biweekly cone beam CT verification of the setup during the entire course of treatment. Tolerance limits were set at 3 mm. The radiation plans for radically treated patients were analyzed taking data from our respective treatment planning systems. Results of weekly radiation reviews for toxicity were included.

We followed a uniform policy of chemotherapy in the concurrent and palliative/adjuvant setting. The details are mentioned in [Table 1]. Treatment charts were reviewed for the chemotherapy employed and toxicity was noted accordingly.
Table 1: Details of radiation and chemotherapy delivered

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 » Results Top


We found a total of nine patients. All were primary malignant tumors arising from the trachea. The demographic details are tabulated in [Table 2]. The median follow-up was 28 months ranging from 2 to 158 months. Median survival has not been reached.
Table 2: Demography and overall survival

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All patients treated with radical intent except one, were treated with 3DCRT. One patient treated radically, received the first phase with conventional treatment planning (40 Gy in 20 fractions by fluoroscopic simulation) followed by a 3DCRT boost. Consequently, the dose-volume parameters were not included for this patient. The details of radiation delivered and the relevant dose-volume parameters are tabulated in [Table 1]. The homogeneity index (HI) (D2/D98) and conformity index (CI) (volume of body receiving prescription dose divided by volume of PTV receiving prescription dose) for each plan was evaluated. The median HI was 1.36 (range: 1.10-1.59) while the median CI was 1.26 (range: 1.0-1.42). All organs at risk received radiation within their tolerance limits. Another patient was treated with re-irradiation, 13 years after radical radiation up to 60 Gy delivered with conventional techniques. Subsequently, dose-volume parameters for the re-irradiation treatment were not included.

Three patients received concurrent chemotherapy with Paclitaxel and Carboplatin. Two patients received palliative chemotherapy with the same regimen. Only one patient received a single cycle of Docetaxel and Capecitabine as second line palliative therapy and progressed thereafter.

Given the esophageal extension of disease in all our radically treated patients, it was our policy to prophylactically place a nasogastric feeding tube before the commencement of radical chemoradiation. Thus, we were able to maintain nutrition during radical treatment. The feeding tube was removed at 6 weeks after the end of our treatment, when all our patients were able to take semisolid enteral feeds by mouth. Acute esophageal toxicity was a maximum of grade 3 (Radiation Therapy Oncology Group) in one patient as evidenced by local pain controlled with narcotic analgesics. None of the patients had hematological toxicity during radical treatment. One patient developed a benign esophageal stricture at 1 year of follow-up that required esophageal balloon dilatation. Thereafter, his swallowing was normal. As of last follow-up, none of the other patients have had late esophageal toxicity.

Three patients had extensive local disease and were offered palliative radiation. All these patients were above 60 years of age. Two were given 20 Gy in five fractions (one fraction a day for 5 days) whereas one patient received 20 Gy in four fractions (each fraction delivered weekly). The palliative radiation was tolerated well. Although two patients did not return for follow-up, one patient continues to have good symptomatic benefit for more than a year.

The course of two patients treated with palliative chemotherapy is instructive for response. One patient had a local and distant relapse after 18 months of radical treatment and was offered combination chemotherapy with Paclitaxel and Carboplatin. He had good symptomatic relief and a radiological partial response after 3 cycles. He progressed on further chemotherapy with the same regimen. He failed further chemotherapy with Docetaxel and Capecitabine. He continued to have short term symptomatic relief with palliative radiation for local disease and bony metastasis. Another patient was not eligible for upfront surgery. He was treated with 6 cycles of Paclitaxel and Carboplatin, with a partial response which was consolidated with 60 Gy of radical radiation alone. He relapsed at 2 years with locoregional disease which was further palliated with 3 cycles of Paclitaxel and Carboplatin and intermittent endoscopic debulking of the tumor. This resulted in stable disease. Currently, this patient continues to receive the same regimen with addition of Cetuximab and has a follow-up of 5 years, at last follow-up.


 » Discussion Top


When possible, tracheal malignancies have been treated primarily with surgery. Adjuvant radiation follows in most cases since surgery is often compromised by anatomical constraints. This approach has offered less than 15% survival for more than a year. [1] However, radiation alone has also shown promise as a standalone treatment option. In a retrospective analysis, Mornex et al. [1] concluded radiation alone to be a good alternative to surgery. Their study identified performance status and radiation dose (greater than 60 Gy) as significant prognostic factors. With a mean follow up of 141 months, their series showed overall 1-, 2-, and 5-year survival rates of 46%, 21%, and 8%, respectively. Makarewicz and Mross [2] arrived at similar conclusions in their study of 23 patients, where a dose escalation combination using external beam radiation and brachytherapy was utilized. Almost a third achieved local control, and this was more frequent in patients receiving more than 60 Gy. Their mean survival was 26 and 7.2 months for the curative and palliative group, respectively. Chao et al. [3] identified factors prognostic of survival in patients treated with radiotherapy. In their study of 42 patients, univariate analysis revealed performance status, weight loss and lymph node or distant metastatic involvement as significant prognostic factors. Similar to the other studies, doses above 50 Gy were associated with improved survival. However, the authors attribute this to patient selection. Interestingly, none of our radically treated patients had locoregional adenopathy at baseline.

Jeremic et al. [4] explored correlation between dose and outcome in a retrospective study of 22 patients. Their median survival was 24 months and 5 year survival was 27%. Mediastinal lymphnode involvement was a bad prognostic factor. Survival was not significantly different at a dose of 70 Gy versus 60 Gy, whereas tracheal toxicity was.

The largest series reporting on outcomes using radiation therapy alone utilized portals which included the gross tumor along with the adjacent superior mediastinum and supraclavicular lymphnodes. [1] Brachytherapy was also used. This approach had an overall response rate of 89%. The pattern of failure was predominantly local (73%). Our approach has been to include the gross tumor only and exclude elective irradiation of the adjacent nodal areas. This approach combined with conformal three dimensional radiation planning perhaps helps to achieve dose escalation while limiting toxicity. Considering the pattern of relapse in our series, elective nodal irradiation is probably of no benefit for the adenoid cystic histology. Two patients relapsed on follow-up, and they had squamous histology. The pattern of relapse was predominantly locoregional. Elective nodal irradiation might have a role for this subset of patients.

Dose escalation and a dose-response relationship are clearly established in literature. However, higher doses came at the cost of higher toxicity. The addition of intraluminal brachytherapy as a means of dose escalation has been cited in literature. [5] Although this is a good modality for palliation in the recurrent setting, modern conformal approaches might obviate the need for this practice at least in the radical setting. We believe dose escalation to be possible with minimal toxicity using our conformal approach as demonstrated in our series. No life threatening toxicities have been noted till last follow up. This includes a patient who underwent conformal re-irradiation for a recurrent tumor.

Xie et al. [6] have recently demonstrated a survival benefit for radiation in tracheal tumors. Radiation was particularly associated with better survival for the squamous cell histology and patients who did not undergo resection.

Another approach toward therapy intensification is the addition of concurrent chemotherapy with radiation. Concurrent chemotherapy may be of special significance as squamous cell carcinoma (SCC) is the predominant histology. It may also benefit the subset of patients with adenoid cystic carcinoma (ACC) which tends to metastatize late. Concurrent chemotherapy is well established in the radical treatment of locally advanced head and neck cancer and lung cancer. This approach may well be of value in the treatment of tracheal carcinomas. Available literature is in the form of case reports. Concurrent chemoradiation with Paclitaxel and Carboplatin has been used for definitive management. [7],[8] Palliative chemotherapy for tracheal malignancies is an unexplored area. Although radiation therapy is well established for palliation, chemotherapy responses have received scarce attention. Paclitaxel and Carboplatin seem to have activity in the metastatic setting as evidenced by two of our cases, one of which continues to enjoy good palliation of his symptoms even at re-challenge.

Various agents have shown activity in ACC of salivary gland origin. [9] the combination of Paclitaxel and Carboplatin showed a 20% response rate. There is no specific chemotherapy regimen for SCC. The combination of Paclitaxel and Carboplatin however, has shown activity. [8]

Lastly, concern has been raised about the radiation dosimetry involving air-filled cavities. [10] Air-filled cavities produce areas of electronic disequilibrium near the air-tissue interface. Waldron et al. [11],[12] reported significant local recurrence rates of malignant disease in two separate retrospective trials involving sinus cancers treated with curative intent. Concern was expressed about the risk of local control of disease due to potential under dosing of the target due to physical uncertainties of the dose distribution achieved in irradiating large air cavities. Joshi et al. [10] have recently demonstrated how the magnitude of dose reduction near air-water interfaces decreases with the increase in the number and size of radiation beams, and increases with photon energy. They further demonstrate the absence of interface dose reductions in 3DCRT techniques. Also, Monte Carlo simulation may better estimate the doses delivered at these interfaces. Hence, modern conformal radiation delivery may have the added advantage of reducing dose uncertainty in tracheal tumors where this problem almost always exists.


 » Conclusions Top


Tracheal tumors present a rare and difficult challenge to the oncologist. Adjuvant treatment modalities have improved dramatically with time and are being increasingly employed. Our series demonstrates that adjuvant chemoradiation may play a significant role in the management of this malignancy. It may be postulated that elective regional nodal irradiation is useful for squamous cell histology whereas only the gross disease can be irradiated for the adenoid cystic histology. The combination of Paclitaxel and Carboplatin has shown activity for both squamous and adenoid cystic histology and deserves further study.

 
 » References Top

1.
Mornex F, Coquard R, Danhier S, Maingon P, El Husseini G, van Houtte P. Role of radiation therapy in the treatment of primary tracheal carcinoma. Int J Radiat Oncol Biol Phys 1998;41:299-305.  Back to cited text no. 1
    
2.
Makarewicz R, Mross M. Radiation therapy alone in the treatment of tumors of the trachea. Lung Cancer 1998;20:169-74.  Back to cited text no. 2
    
3.
Chao MW, Smith JG, Laidlaw C, Joon DL, Ball D. Results of treating primary tumors of the trachea with radiotherapy. Int J Radiat Oncol Biol Phys 1998;41:779-85.  Back to cited text no. 3
    
4.
Jeremic B, Shibamoto Y, Acimovic L, Milisavljevic S. Radiotherapy for primary squamous cell carcinoma of the trachea. Radiother Oncol 1996;41:135-8.  Back to cited text no. 4
    
5.
Thotathil ZS, Agarwal JP, Shrivastava SK, Dinshaw KA. Primary malignant tumors of the trachea: The tata memorial hospital experience. Med Princ Pract 2004;13:69-73.  Back to cited text no. 5
    
6.
Xie L, Fan M, Sheets NC, Chen RC, Jiang GL, Marks LB. The use of radiation therapy appears to improve outcome in patients with malignant primary tracheal tumors: A SEER-based analysis. Int J Radiat Oncol Biol Phys 2012;84:464-70.  Back to cited text no. 6
    
7.
Allen AM, Rabin MS, Reilly JJ, Mentzer SJ. Unresectable adenoid cystic carcinoma of the trachea treated with chemoradiation. J Clin Oncol 2007;25:5521-3.  Back to cited text no. 7
    
8.
Joshi NP, Haresh KP, Das P, Kumar R, Prabhakar R, Sharma DN, et al. Unresectable basaloid squamous cell carcinoma of the trachea treated with concurrent chemoradiotherapy: A case report with review of literature. J Cancer Res Ther 2010;6:321-3.  Back to cited text no. 8
    
9.
Laurie SA, Ho AL, Fury MG, Sherman E, Pfister DG. Systemic therapy in the management of metastatic or locally recurrent adenoid cystic carcinoma of the salivary glands: A systematic review. Lancet Oncol 2011;12:815-24.  Back to cited text no. 9
    
10.
Joshi CP, Darko J, Vidyasagar PB, Schreiner LJ. Dosimetry of interface region near closed air cavities for Co-60, 6 MV and 15 MV photon beams using Monte Carlo simulations. J Med Phys 2010;35:73-80.  Back to cited text no. 10
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11.
Waldron JN, O′Sullivan B, Warde P, Gullane P, Lui FF, Payne D, et al. Ethmoid sinus cancer: Twenty-nine cases managed with primary radiation therapy. Int J Radiat Oncol Biol Phys 1998;41:361-9.  Back to cited text no. 11
    
12.
Waldron JN, O′Sullivan B, Gullane P, Witterick IJ, Liu FF, Payne D, et al. Carcinoma of the maxillary antrum: A retrospective analysis of 110 cases. Radiother Oncol 2000;57:167-73.  Back to cited text no. 12
    



 
 
    Tables

  [Table 1], [Table 2]

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