The survey went out to a total of 24 physicians representing medical oncology (n=13), radiation (n=7) and surgical thoracic oncologists (n=4) and all responded. Thirteen were male and 11 were female; all had been in practice for over 5 years. All medical oncologists practiced general rather than thoracic specific oncology.
Surgical Approaches:
The case volume varied between our surgeons ranging from less than 4/month to over 20/month. Although all patients in Georgia have access to surgery, it is not performed at diagnosis for the vast majority due to diagnosis at a later stage. Three of the four surgeons did not have access or use a MDT conference.
Regarding the treatment of early stage LC, only 2 performed video-assisted thoracoscopy (VATS). Three of them performed systematic lymphadenectomy; the fourth preferred lymph node (LN) sampling. When asked about the role of surgery in oligometastatic NSCLC, two did not offer surgery and two did so but only in selected patients, mostly in case of single brain or adrenal metastasis. In addition, two offered surgery for patients presenting with bulky T4 NSCLC, while the other two did not. All surgeons would consider neoadjuvant chemotherapy (CHT) or RT-CHT, followed by either pneumonectomy or lobectomy/bilobectomy in medically fit patients.
There are extremely few cases of early stage SCLC in the country and two of the four surgeons reported seeing less than 3 surgical cases/annually. Both do not offer surgery for SCLC.
Systemic Therapy:
All medical oncologists (n=13) reported a limited ability to prescribe targeted treatments, mostly due to the costs; however, chemotherapy is widely available. While all had access to diagnostic biomarkers for lung cancer, testing for epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK) and programmed death ligand-1(PD-L1) was not routinely used due to limitation in access to modern therapeutics. Notably, while molecular testing is available, it is performed on a send-out basis.
Despite these limitations, all medical oncologists (13 out of 13) would recommend EGFR testing, with ALK and ROS1 testing recommended by 8 and 7 clinicians, respectively. Nine felt testing for PD-L1 over expression was warranted; only two of them recommended testing for KRAS mutation. [Fig.1].
Patients with driver mutation can access to several TKIs within the public health system, albeit with only partial funding. We found that only approximately 16% (range, 0-30%) of EGFR mutated patients received first-generation TKIs; with even less access to 2nd or 3rd generation agents.
In our survey, five out of 13 respondents had no access to clinical trials. Most clinical trials were evaluating immunotherapy, with an average of two per center (range, 0 to 5). We identified that a high percentage (39.5%) of patients with lung cancer accessed these opportunities (range, 0-95%). Only a very little number of patients receive immunotherapy outside of clinical trials- average, 2 patients (range, 0-5) annually reflecting the lack of access to immunotherapy drugs.
The survey reported almost universal administration of platinum-based therapy for patients with wild type, advanced-stage NSCLC in Georgia. Paclitaxel/carboplatin, cisplatin/gemcitabine, cisplatin/pemetrexed, carboplatin/docetaxel, or carboplatin/pemetrexed were regimens in common use [Fig. 2].
For metastatic squamous cell NSCLC most frequently used regimen in 1st line setting is cisplatin/gemcitabine (76%), followed by paclitaxel/carboplatin (38%). In non-squamous histology most institutions use paclitaxel/carboplatin (54%), and then platinum compounds with pemetrexed (23%).
Platinum plus etoposide chemotherapy is the cornerstone regimen in the treatment of patients with SCLC. Cisplatin with etoposide is mostly used combination in both LD- and ED-SCLC, 77% and 54% respectively. In most institutions platinum/etoposide CHT combined with thoracic RT is the choice for patients with limited disease (LD SCLC), while CHT alone is used in patients with extensive disease (ED SCLC) followed by TRT in responders. Other regimens used in ED-SCLC in first line setting are combination of carboplatin/etoposide and cisplatin with either topotecan or irinotecan.
Radiation Therapy:
Seven of 13 institutions offered RT. Six out of 7 responding institutions house megavoltage linear accelerators (Linacs), while only one institution houses a single Cobalt machine capable of performing 3D RT. These external beam machines are coupled with brachytherapy and fully equipped medical physics equipment, in addition to available CT and MRI scans. Two institutions have access to PET-CT for treatment planning. None of the 7existing RT departments use brachytherapy in the treatment of lung cancer, either alone or in combination with other treatment modalities. The vast majority of institutions use triple A (AAA) planning algorithms for the treatment of lung cancer. All institutions frequently use adaptive RT, re-planning being done after two/thirds to three/fourths of the planned total RT dose being given, if satisfactory response to initial part of the RT is observed. Two institutions having access to PET-CT occasionally use it for adaptive RT planning.
For people with early (Stage I-II) NSCLC,all institutions use 3D conventionally fractionated (CF) RT.Indications to use RT in this setting include technically operable but medical inoperable cases, those deemed elderly/frail as well as occasional patient who refuse surgery. Total doses of RT range from hypofractionated 55 Gy in 20 daily fractions to CF 60-70 Gy in 30-35 daily fractions. Target volumes always include visible tumor with or without lymph nodes and only in one case incorporate elective nodal irradiation. Three out of seven departments use stereotactic body RT (SBRT) in Stage I NSCLC with total doses given ranging from 27 Gy in 3 fractions to most commonly given 50 Gy in 5 fractions but also including 60 Gy in 8 fractions, all depending on the tumor location. Various means of tumor motion control is in use in these centers and is considered mandatory. Postoperative RT is instituted after surgery in early stage NSCLC due to various reasons such as positive surgical margins (R+), pN2, extracapsular extension (ECE) in all institutions but at an extremely low rate. Total RT doses are 50-54 Gy given with a CF and only two departments use 60 Gy CF. In locally advanced (Stage III) NSCLC, four departments would not consider any surgical multimodality approach, while of the other three, two specified patients with low tumor volume or single mediastinal LN station as potential candidates for induction CHT or RT-CHT followed by surgery as their treatment option. Of the latter group, one even specified as potentially suitable patients those with bulky tumors presumably not being curable with exclusive high-dose concurrent RT-CHT. In a non-surgical scenario, 5 out of 7 departments would prefer concurrent RT-CHT, while one would also consider induction CHT followed by either RT or concurrent RT-CHT depending on the patient’s PS. When however, asked when they would consider induction CHT followed by either RT or concurrent RT-CHT, they mostly preferred induction CHT in bulky T and/or N due to fear of concurrently giving CHT with “too” large RT fields leading to more toxicity as well as when extensive symptoms and poor PS are expected to resolve with CHT before RT. Contrary to these, the responders would consider concurrent RT-CHT in non-bulky tumors and young and fit patients with a good PS. Total doses and fractionation used in this setting included CF 60-70 Gy always given on all visible tumors only. In cases of Pancoast tumors, preferred approach in all but one department would be exclusive concurrent RT-CHT (i.e. no surgery at all), and only one institution would consider preoperative RT-CHT followed by surgery as an option. When asked about surgery in cases of bulky tumors invading major intrathoracic structures, none of the respondents specified it would be an agreeable solution on a MDT meetings. In symptomatic Stage IV patients, responders would treat all existing symptoms. Thoracic RT would be used with total doses of 20 to 50 Gy given in 5 to 20 fractions and only a single department would consider 60 Gy in 30 fractions in this setting. Four out of seven institutions recognized specifics of “oligometastatic” disease, but the number of metastasis deemed as appropriate for this designation varied between up to 3 and up to 5. Dose and fractionation of oligometastases greatly varies. Brain metastases were mostly treated with stereotactic radiosurgery (SRS) (15-24 Gy in a single fraction), while non-brain metastases located in various organs and tissues were treated with dose/fractionation regimens from 18-24 Gy in 1-3 fractions to 27 Gy in 3 fractions or to30 Gy in 6 fractions or even to 50 Gy given in either 5 or 10 fractions, given sometimes on alternate days. When asked in which cases of LC metastatic to lung parenchyma they would consider surgery as the treatment of choice, two departments would never suggest it, other citing ipsilateral metastases only, fit patients only, single ipsilateral/lobar metastases and primary controlled with a few (though not specified) lung metastases.
In LD SCLC domain, five departments would consider starting concurrent part of the combined RT-CHT approach during either the first or the second cycle of CHT, one department preferring the third cycle of CHT while only one department opted for sequential CHT-RT approach with RT starting afther the fourth CHT cycle. In cases when RT starts with the >2 cycle of CHT, only one department would use pre-CHT volumes to be treated. Dose and fractionation included either 45 Gy in 30 fractions in 15 treatment days (1.5 Gy bid) (n=3) or 60-70 Gy in 30-35 daily fractions (n=2) while two departments were using both regimens without clearly specifying preferences for the use of either of these two. All seven departments use prophylactic cranial irradiation (PCI) after the end of complete RT-CHT, allowing one month after it for the evaluation of response. Dose of 25 Gy in 10 daily fractions was used in six departments of which only one allowed 20 Gy in 5 daily fractions, while the sole RT department practices 30 Gy in 10 daily fractions. All seven departments use thoracic RT in ED SCLC and do that after 3 cycles of CHT (n=3) or after 4-6 cycles of CHT (n=4). Four out of six would use thoracic RT given concurrently with CHT, two departments would practice sequential CHT and RT approach, and one department would use both. Thoracic RT doses and fractionation used in this setting included 45 Gy in 15 daily fractions (n=2), 46-54 Gy in 23-24 daily fractions (n=1), 30 Gy in 10 fractions (n=2), 60 Gy in 30 fractions (n=1), 30 to 40-45 Gy in 10-15 fractions (n=1) and 50-60 Gy in 2 Gy daily fractions (n=1). Target volumes included visible tumor in six and pre-CHT volumes in one case. Three institutions do not use PCI after RT-CHT and four use it after RT-CHT was finished (allowing a gap of 1 month), PCI being given in cases of CR at both intrathoracic and distant sites. When used PCI was given in 25 Gy in 10 daily fractions while only one department also allowed 20 Gy in 5 daily fractions.