The benefits of locally-applied therapies in lung cancer

Only 16% of all new lung cancer diagnoses are localized cancer (T1, N0), which have 5-year survival rates of 68% to 92%, depending on the size and location of the lesion.1,2 Until recently, there were very few practical ways to localize lung lesions and provide minimally-invasive, local therapy. Therefore, the guideline-directed first-line treatment for localized lung cancer is surgical resection by lobectomy.3,4 Some patients may be unable to tolerate a lobectomy and alternative procedures can be conducted, such as limited resection or stereotactic body radiation therapy (SBRT), though these options have inferior outcomes compared to lobectomy.3-5

Another option for patients who are unable or unwilling to undergo lobectomy is minimally-invasive, locally-applied therapy. Local therapies are only effective when the lesion(s) can be localized accurately.6 Historically, it has been challenging to localize small lesions;therefore, local therapies have often not been used in eligible patients.

Recently, technology developments, such as Body Vision’s real-time, image-guided navigation LungVision™ platform, are better enabling local therapies as they allow localization of lung lesions with high accuracy. The lesions are accessed through natural body openings with delivery catheters placed at the desired location inside the lesion. The LungVision™ platform is illuminating small pulmonary nodules to make locally-applied therapeutic options more readily available.

The general benefits of a locally-applied therapy for lung cancer (primary or metastatic) over a systemic therapy (such as chemotherapy, targeted immunotherapy, or radiation) are that the tissue exposed to the therapy is much more restricted, substantially reducing systemic side effects.7,8 In addition, a locally-applied therapy can be applied through percutaneous access, reducing some of the morbidity associated with surgical resection.7 Locally-applied therapies are a suitable option for an estimated 30% of patients with early stage lung cancer who do not undergo surgery.9

Recently, several modalities of local therapies for lung cancer have been investigated. Lung cancer ablation uses directed energy to kill malignant tissue and cause intentional scaring. Radiofrequency ablation (RFA) uses electromagnetic energy to induce thermal injury in the lung lesion.5,10 Benefits of RFA over surgical resection include outpatient treatment, no change in pulmonary function tests, and limited damage to surrounding tissues.11 Complications can occur during or after RFA, including pneumothorax, hemoptysis, bronchopleural fistula, or rib fracture.5,10,12 RFA may not be effective on lung lesions > 3 cm in diameter or those located near blood vessels11,13 Three-year local control rates for RFA are approximately 80-95%.5,13,14

Microwave ablation is similar to RFA in that it uses electromagnetic energy to cause thermocoagulation of the target lesion, with minor modifications to the procedure and devices.5,10 Microwave ablation may have advantages over RFA, such as improved energy deposition in the tissue, a larger ablation zone, shorter time to achieve sufficient ablation, and possibility of ablation closer to blood vessels; the complications from the procedure are similar to RFA.5,10,15 Data is more limited on microwave ablation, but the procedure appears to have similar outcomes to RFA for local control and survival.5

Lasers can be used to increase the local temperature of tissue and cause necrosis and ablation.7 Compared to other locally-applied therapies in lung cancer, possible benefits of laser thermal therapy include ease of introducing a laser fiber into the tissue, cost effectiveness of the materials, and possibly improved therapeutic success and tumor control, though the data on laser thermal therapy is limited.16

Cryoablation uses negative thermal energy (cold) to rapidly freeze and thaw the tissue to cause cell death.5,10 Cryoablation is most useful for central lung lesions < 3 cm in diameter.5,17 Because there is a delay between the cryoablation procedure and necrosis, the procedure doesn’t immediately remove an obstructive lesion.5 Rates of successful outcomes are similar with cryoablation, and it carries similar risks to RFA and MWA.5,10,17

Photodynamic therapy (PDT) involves systemic delivery of a photosensitizing agent and local application of visible light at the lung lesion to activate the photosensitizing agent, which produces singlet oxygen and cytotoxic agents.5 Complications of photodynamic therapy can include hemorrhage, respiratory compromise, and skin burns.5 PDT is best used for lung lesions ≤ 1 cm-diameter as sufficient light penetration becomes an issue for larger lesions.5 Complete response rates for PDT in early stage lung cancer range from 62% to 100%.5

No randomized, controlled trials have compared surgery alone to radiation alone or to locally-applied ablation therapies, so it is challenging to make direct comparisons between the outcomes of each treatment modality.3,8

Locally applied therapies provide options to patients unwilling or unable to undergo lobectomy or limited resection and may offer improved local control and survival compared to previous options. With accurate localization of lung lesions, local therapies can be applied effectively, with the goal of improving survival for patients with lung cancer.

REFERENCES

1.         National Cancer Institute, Surveillance, Epidemiology, and End Results Program. Cancer Stat Facts: Lung and Bronchus Cancer.  https://seer.cancer.gov/statfacts/html/lungb.html. Accessed Accessed September 27, 2018.

2.         American Cancer Society. Non-small cell lung cancer survival rates, by stage. December 18, 2017; https://www.cancer.org/cancer/non-small-cell-lung-cancer/detection-diagnosis-staging/survival-rates.html. Accessed September 27, 2018.

3.         Howington JA, Blum MG, Chang AC, Balekian AA, Murthy SC. Treatment of Stage I and II Non-small Cell Lung Cancer - Diagnosis and Management of Lung Cancer, 3rd ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2013;143:e278S-e313S.

4.         Postmus PE, Kerr KM, Oudkerk M, et al. Early and locally advanced non-small-cell lung cancer (NSCLC): ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2017;28:iv1-iv21.

5.         Jones GC, Kehrer JD, Kahn J, et al. Primary treatment options for high risk/medically inoperable early stage NSCLC patients. Clin Lung Cancer. 2015;16:413-430.

6.         Khan KA, Nardelli P, Jaeger A, O’Shea, Cantillon-Murphy P, Kennedy MP. Navigational bronchoscopy for early lung cancer: A road to therapy. Adv Ther. 2016;33:580-596.

7.         Pereira PL, Salvatore M. Standards of practice: Guidelines for thermal ablation of primary and secondary lung tumors. Cardiovasc Intervent Radiol. 2012;35:247-254.

8.         Smith SL, Jennings PE. Lung radiofrequency and microwave ablation: A review of indications, techniques and post-procedural imaging appearances. Br J Radiol. 2015;88:20140598.

9.         Bach PB, Cramer LD, Warren JL, Begg CB. Racial differences in the treatment of early-stage lung cancer. N Engl J Med. 1999;341:1198-1205.

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11.       Dupuy DE, Fernando HC, Hillman S, et al. Radiofrequency ablation of stage ia non–small cell lung cancer in medically inoperable patients: Results from the American College of Surgeons Oncology Group Z4033 (Alliance) trial. Cancer. 2015;121:3491-3498.

12.       Welch BT, Brinjikji W, Schmit GD, et al. A national analysis of the complications, cost, and mortality of percutaneous lung ablation. J Vasc Interv Radiol. 2015;26:787-791.

13.       de Baere T, Farouil G, Deschamps F. Lung cancer ablation: What is the evidence? Semin Intervent Radiol. 2013;30:151-156.

14.       Bi N, Shedden K, Zheng X, Kong F. Comparison of the effectiveness of radiofrequency ablation with stereotactic body radiation therapy in inoperable stage i non-small cell lung cancer: A systemic review and meta-analysis. Pract Radiat Oncol. 2013;3:S19.

15.       Healey TT, March BT, Baird G, Dupuy DE. Microwave ablation for lung neoplasms: A retrospective analysis of long-term results. J Vasc Interv Radiol. 2017;28:206-211.

16.       Rosenberg C, Puls R, Hegenscheid K, et al. Laser ablation of metastatic lesions of the lung: Long-term outcome. AJR Am J Roentgenol. 2009;192:785-792.

17.       Wang H, Littrup PJ, Duan Y, Zhang Y, Feng H, Nie Z. Thoracic masses treated with percutaneous cryotherapy: Initial experience with more than 200 procedures. Radiology. 2005;235:289-298.