THE FUTURE IN TREATMENT
Although complete surgical removal of primary lung tumors before metastasis offers the best hope for a cure, several promising
treatment modalities are on the horizon.
Intensity-modulated radiation therapy
An alternative to conventional lung lobectomy in companion animals is the use of intensity-modulated radiation therapy (IMRT).
This treatment modality allows the delivery of curative-intent megavoltage radiation to the neoplastic lesion. Excessive delivery
of radiation to normal tissues is minimized by collimating multiple treatment beams in the radiation field to conform three-dimensionally
to the geometry of the cancerous mass.52
In a case study, the effectiveness of IMRT for treating a primary bronchoalveolar carcinoma in a dog was assessed by using
positron emission tomography combined with CT. After treatment with IMRT, the dog survived 22 months, only to be euthanized
for clinical signs considered unrelated to the primary lung tumor or treatment with IMRT. This anecdotal case report demonstrates
favorable clinical outcomes with combination IMRT and positron emission tomography and CT for the treatment and response-assessment
of a primary lung tumor in a dog.52
Another promising alternative to surgical removal of primary lung tumors is radiofrequency ablation (RFA). A heating electrode
is directly inserted into the tumor percutaneously under the guidance of CT, and alternating electrical currents are passed
through the electrode into the neoplastic mass with the intent of inducing tumor cell necrosis.
In a study using animal models, transmissible venereal tumor fragments were injected into the lungs of five dogs, and the
patients were subsequently subjected to site-directed RFA. After treatment, the dogs were euthanized, and lung lesions were
histologically evaluated. All tumor lesions demonstrated complete thermal coagulative necrosis with no evidence of viable
tumor cells. The damage to normal lung parenchyma involved only a narrow zone of hemorrhagic necrosis surrounding each ablated
The efficacy of RFA on primary pulmonary masses suggests that animals with metastatic pulmonary nodules may also benefit from
this treatment modality. Such a supposition is supported by one study in which electrode placement in the epicenter of the
cluster of nodules was adequate for complete nodule ablation.53
The localized delivery of chemotherapeutic agents or cytokines to the thoracic cavity or lung parenchyma may allow for enhanced
anticancer effects within the immediate tumor microenvironment.
Intracavitary chemotherapy. The clinical effectiveness of intracavitary cisplatin administration (50 mg/m2) has been investigated in six dogs with malignant cavitary effusions.54 In three dogs with pleural mesothelioma, complete resolution of cancerous effusions was achieved after a maximum of two
treatments. These favorable anecdotal findings warrant further exploration of intracavitary chemotherapeutic strategies for
managing the clinical consequences associated with primary or metastatic lung tumors.
A more recent study evaluated the effectiveness of intracavitary mitoxantrone or carboplatin for treating thoracic or abdominal
carcinomatosis, sarcomatosis, or mesothelioma in patients with and without malignant effusions. In dogs treated with intracavitary
chemotherapy, the median survival time was 332 days, compared with only 25 days in untreated dogs.55 These findings derived from a small population of cancer-bearing dogs also suggest that intracavitary chemotherapy exerts
some beneficial anticancer effects.
Inhaled chemotherapy. Although intracavitary chemotherapy may increase the concentration of drug within the pleural space and at the visceral surface
of the lung, the attainment of higher drug concentrations within the pulmonary parenchyma is better achieved through inhalation
therapy. In a recent study, either doxorubicin or paclitaxel was delivered by aerosolization to 28 dogs with either primary
or metastatic pulmonary neoplasia.56 Tumor regression occurred in 25% of dogs treated, with one patient demonstrating partial regression of metastatic hilar
lymphadenopathy. Although typical toxicities of systemic doxorubicin chemotherapy (myelosuppression, nausea, and vomiting)
were not seen, acute local pulmonary effects (intermittent, nonproductive cough) were noted in about half the dogs.
An important finding in this study was that dogs receiving inhalation doxorubicin on the same day as systemic doxorubicin
did not experience any increase in systemic toxicosis, suggesting that inhaled doxorubicin exerted its effects locally.56 Thus, combining two different routes of chemotherapy administration may exert superior anticancer effects without added
Inhaled cytokines. Similar to the delivery of inhaled chemotherapy, the aerosol delivery of liposome-encapsulated IL-2 produced clinical responses
in dogs with osteosarcoma metastases, with two of four patients achieving complete remission of their metastatic disease.57 Disappointingly, two dogs with primary lung tumors did not respond as well, with one achieving stable disease and the other
experiencing progressive disease. Nonetheless, this study demonstrates that antitumor immune responses may be augmented through
the delivery of aerosolized cytokines.57