The Second Cuneo Lung Cancer Conference finally ended after many hours of dedicated effort. It was held in Terme di Valdieri, a thermal mountain resort in the Maritime Alps of the Cuneo province (Italy). From Saturday, June 20, 1998, to Wednesday, June 24, any possible option for the treatment of the loco-regionally-advanced non-small cell lung cancer (NSCLC) was reviewed, critically reconsidered, challenged, and compared to each other. This report will highlight selected aspects of the scientific, social, and cultural program. It will summarize the lectures in the scientific program and the opinions prevailing among the participants. A few personal reflections by the Conference’s organizer will conclude the report.

In the last few years, a new wave of optimism has spread among thoracic oncologists (1). With the marketing of new active drugs, the increasing sophistication in radiation technology, and the optimization of multidisciplinary approaches, response rates up to 70% and pathologically confirmed complete responses have become possible, even in NSCLC. In loco-regionally-advanced NSCLC, in particular, the combination of chemotherapy and radiotherapy may be highly efficacious. Opinion leaders (2) and authoritative guidelines from cancer (3) and respiratory (4) societies all have endorsed this idea. One could argue that the only remaining question is whether the best chemoradiation treatment of today is as active in NSCLC as the chemotherapies of the 1970s were in small-cell lung cancer (SCLC). In SCLC, no control studies were ever required to accept chemotherapy as the standard…

The idea that there is a standard treatment for the loco-regionally-advanced NSCLC and that such a standard is chemoradiation is contrasted by at least two considerations. First, there is a lack of univocal behavior in everyday practice. This is evident considering the wide range of physicians’ preferences and the diversity of patterns at the patient’s bedside, in clinical research, and even among nations and specialties (5). Second, evidence-based medicine requires multiple randomized controlled studies (and one or more meta-analyses) that positively tested the new innovative treatments in order to accept them as the new standard. Chemoradiation is an innovative treatment modality. It has been favorably compared with radiation alone in multiple randomized trials and in one meta-analysis (6). Yet one can question: "Has it been compared reliably also with the baseline policy of treating patients with only symptomatic relief and support care?" and: "Is such a comparison needed?" The answer to the first question is NO (6). According to one commentator, the answer to the second question is YES (7).

This Conference was a unique event in several ways. It was:

2.1. A MONOTHEMATIC MEETING WITH A THREE-LAYER STRUCTURE

The Conference was restricted to a selected topic of interest to specially trained doctors who were highly competent in their chosen areas of expertise. Its structure was ambitiously designed with the core emphasis on being a highly scientific workshop. Speakers and panelists were the leading experts in individual disciplines. The second was an educational layer. It was designed for medical oncologists and other oncology-related specialists, who would have heard the overviews and discussions, interact with the experts and each other, and then subject the data to close examination and critical reconsideration. The third layer was a new and unusual attempt to include others who, although not technically trained, are deeply involved in the therapeutic decisions-- patients and family members. For the first time, a group of patients, active in ALCASE (Alliance for Lung Cancer Advocacy, Support and Education), participated in a scientific medical program presenting their perception of the disease and its treatment. They were admitted to all scientific sessions, and were asked to pose on table the patients’ perspective. Their participation and comments were particularly relevant to the issue of quality of life. As with any new venture, this was received with a mixed acceptance by the scientific community. The meeting was especially successful in its core layer of quality workshop.

2.2. A CONFERENCE WHERE THE INTERACTION BETWEEN SPEAKERS AND BETWEEN SPEAKERS AND PARTICIPANTS WAS A TOP PRIORITY

The scientific program was designed to expedite the exchange of ideas. Round table discussions were critical means of encouraging discussions and fulfilled their scope in the framework of the workshop. To obtain a "quantification" of the opinions prevailing among participants, a final ballot followed each scientific session. Their results will be presented and discussed later in this report.

2.3. A TRULY INTERNATIONAL EVENT

There were highly respected speakers and participants from four continents and many countries including Australia, Belgium, Brazil, China, South-Chorea, England, Egypt, France, Holland, Italy, Germany, Poland, Switzerland, Turkey, and Unites States….

The following lung cancer experts contributed to the main scientific program:

In this report, a brief summary of the scientific workshop is presented.

Saturday, June 20, 1998, was the arrival day, which was a travel day for most. The Conference officially opened in the late afternoon with a lecture by Prof. Heine H. Hansen. He captured everyone’s attention, depicting the gravity of the world lung cancer epidemic and the paucity of the measures taken from the global community.

The first scientific session started Sunday morning, June 21. It was dedicated to the methodology of assessing and comparing different treatments. From Sunday afternoon to Tuesday 23, four consecutive sessions were dedicated to four different treatment options: chemotherapy alone, radiotherapy alone, chemoradiotherapy, and surgery alone or boosted by adjuvant and neo-adjuvant treatments. For each single treatment modality, the scientific evidence supporting its use was reviewed and critically examined. A brief summary of the five sessions follows:

3.1. SESSION 1: Sunday morning, June 21

EVIDENCE BASED-MEDICINE

Prof. S. Garattini and Dr. J. Tierney chaired the session. Silvio Garattini, head of the Mario Negri Institute of Pharmacology Research, is a member of the European Commission on drug evaluation and market licensing. He has spent his life educating medical students, young doctors, researchers and other health care professionals. Throughout a generous use of the mass media, he has also educated the Italian public, warning for a cautious evaluation of the efficacy of drugs. In his introductory lecture, "From art to science", he gave a historical perspective of the latest pharmacology research and an outlook to the future. The following speech, "Pre-human studies: interpretation of the experimental data", was given by Jens B. Sorensen, medical oncologist and clinical researcher at the Finsen Institute (Copenhagen). The lecture served to reinforce most of the concepts of the prior speaker. It was a privilege to include in the program Chris Williams, head of the International Cochrane Cancer Collaboration Network, prophet of the evidence-based medicine. His talk, "Type, value, and limitations of non-randomized studies, including descriptive reports and historical controls", addressed the role of non-randomized studies in setting the hypothesis. He emphasized their gross overestimate of the efficacy of the new treatment being tested. The following speaker, Paolo Verderio, discussed the principles of statistical inference. In his lecture "Statistical requirements and interpretation of randomized trials", he emphasized the notion of internal and external validity of a clinical trial and the possibility of errors of false positive and false negative conclusions. Jayne F. Tierney, statistician at the British Medical Research Cancer Trial Office, was the following speaker. Her task was to illustrate the "Meta-analysis of randomized trials". She explained that only with the reviewing and analyzing the relevant randomized evidence in a systematic review, or meta-analysis, it is possible to reach sufficient statistical power and the most reliable estimate of the effect. To minimize biases, meta-analysts should centrally check "raw" individual patients' data and ensure that all the relevant, methodologically correct studies are included. Marcello Tamburini, psychologist at the National Tumor Institute in Milan, was called to answer the question "Taken for granted the process of evidence formation, what should we compare to say that treatment 'A' is better than treatment ‘B’?" He stressed the importance of the quality of life in the choice between alternative treatments. Dr. Tamburini magisterially defined the quality of life concept and described its working definition and the modern tools of measure. He concluded: "Survival is the most important outcome in cancer treatment. Nevertheless, survival alone is insufficient; the quality of life and the cost of maintaining and improving it must also be assessed…The choice between alternative treatments often involves a trade off between length and quality of life." The session ended with a round table discussion and a final ballot on three questions:

3.2. SESSION 2: Sunday afternoon, Sunday 21

The first treatment-oriented session started in the afternoon of the same day. Prof. M. Tonato and Dr. G. Buccheri chaired this session.

Maurizio Tonato discussed the chemotherapy of lung cancer in a historical perspective, "From nitrogen-mustards to cis-platinum and beyond." He introduced the themes of the following talks. Andrea Ardizzoni remained strictly within the assigned topic, "News from the lab". He brilliantly reviewed the most modern and promising pathways of research, focusing on four main groups of substances: i. Inhibitors of the matrix metalloproteinases (antimetastatic agents), ii. Anti-angiogenetic drugs, iii. Agents with anti-growth factor activity, and iv. Gene therapy. Jean-Paul Sculier, head of the Lung Cancer Working Party based in Brussels, reviewed the "Activity of drugs recently introduced in the market". He showed highly interesting data obtained from an "ad-hoc" analysis of 55 recently published papers. In each investigation reviewed, at least one of the following drugs had been assessed for response: i. Paclitaxel; ii. Docetaxel; iii. Vinorelbine; iv. Gemcitabine; v. Topotecan; vi. Irinotecan. He concluded with a note of caution: "in spite of the promising activity of most of these drugs, the data available today in the literature are too limited to define exactly their role and their indication in the management of this disease". Jim R. Jett, from the Mayo Clinic, was called to discuss the "Response-survival relationship" and to answer the question as to whether survival rates and treatment responses are correlated to each other. In spite of some negative evidence produced by his accurate analysis of the literature, Dr. Jett was reluctant to provide a clear-cut answer to this important question. Gianfranco Buccheri reviewed the vast literature of "Randomized trials of chemotherapy versus supportive care". Although supportive care studies were never limited to the locally advanced disease, he concluded that: "it is reasonable to admit that chemotherapy is as effective in stage III patients, as it is in the more advanced metastatic setting". Jayne F. Tierney was called to review the " Meta-analysis studies of chemotherapy vs. best supportive care". She accomplished her task, describing in detail the well-known results of the NSCLC Collaborative Group meta-analysis 8. This session and the following ones ended with a round table discussion and a ballot on three questions:

RADIOTHERAPY

The session was opened and chaired by Prof. N. M. Bleehen. Prof. L. Magno co-chaired it. In his excellent introductory lecture, "The escalation of doses and daily fractionation", Norman M. Bleehen reviewed the technical advances made by the radiation technology in the past 50 years. He described the advances made in the X-ray therapy equipment, treatment planning, and quality assurance of the delivered treatment. He placed much emphasis on the recently increased knowledge of radiobiology, which has led to change fractionation schedules and the total dose delivered. His historical overview ranged from the early 40-50 Gy orthovoltage radiation therapy (9) to the recent CHART schedule (three daily fractionations of 1.5 Gy over 12 consecutive days) (10). Paul Van Houtte focused his talk on the "Long-term survival after conventional irradiation therapy". Two-year survival rates, he pointed out, remain poor in most studies and vary significantly from report to report (from 40% of the early retrospective series to 10-20% of the latest, large, prospective trials) (11-13). Explaining these results, he stressed the importance of factors as the loco-regional extent of tumor, the patient’s physical status, and the quality of the radiation technique used. Bringing the essential experience of the RTOG group, William T. Sause discussed the possible survival benefit of high tech irradiation, "Long-term survival with high technology irradiation techniques". He concentrated on 3-D treatment planning and the conformal (to the target volume) irradiation therapy (14). He reviewed the biological assumptions, and the preliminary evidence showing that as dose of 3-D irradiation is increased, median survival is also improved. He described the last initiated RTOG multi-institutional trial, which will randomize patients to several dose levels of 3-D conformal radiotherapy (up to the 90.3 Gy in 42 fractions over 9 to 10 weeks). Anna Gregor was called to assess critically the possible survival benefits of radiotherapy. She reviewed in depth the only three "Randomized studies of radiotherapy vs. best supportive care" (9,15,16). She warned that all three trials are opened to criticism regarding either the technical quality of the radiation treatment, the staging methodology, the patient selection, and reporting standards, or because stopped prematurely. She expressed the opinion that, in spite of the paucity of data, future studies addressing the issue of radiotherapy against best supportive care are very unlikely. Stein Kaasa, reviewing the other three "Randomized studies of radiotherapy vs. chemotherapy" (15,17,18) had to admit that also the evidence concerning the direct comparison of radiotherapy versus chemotherapy is scarce. He concluded that there is no real answer to the question whether radiotherapy or chemotherapy is superior one to another.

A long and 360°-opened discussion followed. Comments were made on:

CHEMO-RADIOTHERAPY

Drs. T. Le Chevalier and P. Van Houtte chaired this session. The first three speakers reviewed the evidence from non-randomized studies. Caro C.E. Koning focused her talk on "Radiosensitization: a myth or a reality?" First, she drew the audience’s attention to reconsider a well-know phenomenon: the in vitro synergism of irradiation and cisplatin. Then, she focused on the analogy with other cancers including the bladder, cervical, esophagus, and head and neck cancer. In such malignancies, she said, cisplatin as a radiosensitizer has been already used with success. Then, she reviewed the conflicting reports regarding NSCLC (11,19-21) and explained the inconsistency with the difficulty in defining remission or local control. She concluded that radiotherapy enhanced by cisplatin could become a reality within a decade. Then, she argued that new clinical trials will be concluded and sensitive patients will be recognized by some biological marker, e.g., the amount of cisplatin adducts. Giorgio V. Scagliotti reviewed "The countless ways in which chemotherapy and radiotherapy have been combined", defining sequential, concurrent, and alternating radiation-chemotherapy administration schedules. Among them, he argued, the concurrent administration could be the most effective, but also the most toxic one. Dr. Scagliotti warned that the optimal combination of chemotherapy agents and delivery schedules and the optimal dose and schedule of irradiation have yet to be determined. To similar conclusions came William T. Sause, discussing the "Efficacy and toxicity of the combined treatment". He emphasized that the combined treatment may remarkably increase pulmonary and esophageal toxicity. He agreed that a new generation of phase III trials would be needed, especially in consideration of the advent of new chemotherapy agents and because of the recent advances in radiation technology. The task of reviewing the vast literature concerning the "Randomized studies of chemo-radiotherapy vs. radiotherapy alone" was assigned to Thierry Le Chevalier. Dr. Le Chevalier started with a masterpiece of anecdotal evidence: the photo of a jockey, who had been treated with radio-chemotherapy alone ten years before, and was pictured while riding his horse in a race. Then, he came back to a more rational but less emotionally stimulating argument. He analyzed the many randomized studies that had tested the addition of a cisplatin-based chemotherapy to thoracic irradiation, and the meta-analysis published in 1995, which had comprehended all of them (8). He suggested that "the combination of chemotherapy and radiotherapy should be considered standard treatment for patients with locally advanced NSCLC able to receive cisplatin-based chemotherapy". Gianfranco Buccheri replaced Dr. David Johnson, suddenly impeded to participate, in his scheduled talk. In contradiction to the previous speaker, Dr. Buccheri pointed out that "Randomized studies of chemoradiotherapy vs. chemotherapy alone or best supportive care" are very few and open to criticisms 6. He concluded that there is no real answer to the posed question. He argued that supportive care, rather than radiotherapy, is the appropriate control treatment for such a disease and that chemoradiotherapy, which was never satisfactorily tested against supportive care, may not be regarded as the standard (6).

The following discussion was stimulating and involved a variety of issues. However, it failed to answer the question implicit in the last presentation--what should be the most appropriate control treatment--, leaving the impression that everyone’s position remained unchanged…

3.5. SESSION 5: Tuesday, June 23

Dr. R. J. Ginsberg and Dr. P. Goldstraw chaired the session. Peter Goldstraw was the first speaker. His talk dealt with the impact of surgery on the natural history of the loco-regionally-advanced NSCLC, "5-year survival rates after surgical resection". Dr. Goldstraw advised his audience to be aware of three important factors. Preoperative staging is an imprecise science. It tends to underestimate the pathological staging revealing a rough guide to the groups of patients suitable for thoracotomy. The inaccuracy of preoperative staging is not fixed, but it becomes progressively larger with advancing stage. The "diminishing denominator" effect, found especially in older series, may have led to the exclusion from analysis of unresectable cases, or postoperative deaths. With this caveat in mind, he admitted that long-term survivals are not encouraging for the surgeon. The improved results of chemotherapy and modern radiation schedules such as CHART, he concluded, have further thrown out the balance away from operation in such subgroups. The impact of postoperative radiotherapy, " 5-year survival rates after surgical resection and adjuvant radiotherapy", was then discussed by Lorenzo Magno. Prof. Magno reviewed the several non-randomized studies that reported a decrease in local relapses and a better survival after radiotherapy. Then, he called attention to the conflicting results of randomized trials. The last are inconclusive for a real advantage, or show a decrease in local relapses that has not been translated into survival benefits. Prof. Magno’s data was timely completed by Dr. Girling, who described the recently published meta-analysis performed by the PORT Meta-analysis Trialists Group, in which a detrimental effect for postoperative irradiation, especially in early stages, was shown 22. The task assigned to Robert J. Ginsberg was to review the evidence on neo-adjuvant treatments, "5-year survival rates after surgical resection and neo-adjuvant chemo-radiotherapy". Dr. Ginsberg’s most important messages are as follows: i. Early phase II trials and small phase III trials suggest that induction therapy yields better results than primary surgery; ii. Comparing induction chemoradiotherapy programs and chemotherapy programs, there may be no added advantage to the radiotherapy component; iii. In most cases, the addition of induction therapy adds some postoperative morbidity but postoperative mortality rates seem acceptable; iv. Brain as the first site of metastasis remains a significant problem; v. The exact role of surgery in patients with clinically evident N2 disease awaits the results of large scale randomized trials specifically addressing this question, now being conducted in North America and Europe. Frank A. Lederle delivered the last lecture, "Does surgery prolong survival?", with a note of caution and possibly skepticism, concerning what is generally accepted as without doubt: the very role of surgery in NSCLC. He reminded everyone that surgery, like radiotherapy, has never been compared with a policy of symptom palliation and supportive care alone (23). He cited a small trial of localized lung cancer, in which surgery and super voltage radiotherapy were compared with no discernable differences (24), and another study, the RTOG 89-01 trial, with quite similar design and results (25). He concluded that a number of randomized trials that could have demonstrated a beneficial effect of surgery in localized NSCLC have failed to do so. While this does not prove surgery to be ineffective, he said, it does challenge the current opinion, especially in loco-regionally-advanced cancers where the benefits of resections are even more unlikely.

During the following discussion, none seemed to be willing to accept Dr. Lederle's provocation about the role of surgery in the initial stages of disease and the focus was returned to the locally advanced condition. The following were the main themes emerged:

1. Carney DN. Non-small cell lung cancer: Slow but definite progress. Semin Oncol 1996; 23 Suppl. 16:5-6.

 2. McNeil C. Combined therapy for lung cancer gets a boost. J Natl Cancer Inst 1996; 88: 1182-1184.

 3. ASCO SPECIAL ARTICLE. Clinical Practice Guidelines for the Treatment of Unresectable Non-Small-Cell Lung Cancer. J Clin Oncol 1997; 15: 2996-3018.

 4. American Thoracic Society, European Respiratory Society. Pretreatment Evaluation of Non-Small-cell Lung Cancer. Am J Respir Crit Care Med 1998; 156: 320-332.

5. Brundage MD, Groome PA, Feldman-Stewart D, Davidson JR, Mackillop WJ. Decision analysis in locally advanced non-small-cell lung cancer: Is it useful. J Clin Oncol 1997; 15: 873-883.

6. Buccheri G, Ferrigno D. Therapeutic options for regionally advanced non-small cell lung cancer. Lung Cancer 1996; 14: 281-300.

 7. Buccheri G. Is there a standard treatment for locally advanced non-small cell lung cancer? Chest 1996; 109: 864-866.

 8. Alberti W, Anderson G, Bartolucci A, et al. Chemotherapy in non-small cell lung cancer: A meta-analysis using updated data on individual patients from 52 randomised clinical trials. Br Med J 1995; 311: 899-909.

 9. Roswit B, Patno ME, Rapp R, et al. The survival of patients with inoperable lung cancer: a large-scale randomized study of radiation therapy versus placebo. Radiology 1968; 90: 688-697.

 10. Saunders M, Dische S, Barrett A, Harvey A, Gibson D, Parmar M. Continuous hyperfractionated accelerated radiotherapy ( CHART) versus conventional radiotherapy in non-small-cell lung cancer: a randomised multicentre trial. CHART Steering Committee [see comments]. Lancet 1997; 350: 161-165.

 11. Schaake-Koning C, Van den Bogaert W, Dalesio O, et al. Effects of concomitant cisplatin and radiotherapy on inoperable non-small cell lung cancer. N Engl J Med 1992; 326: 524-530.

 12. Dillman RO, Seagren SL, Propert KJ, et al. A randomized trial of induction chemotherapy plus high-dose radiation versus radiation alone in stage III non-small-cell lung cancer. N Engl J Med 1990; 323: 940-945.

 13. Sause WT, Scott C, Taylor S, et al. Radiation Therapy Oncology Group (RTOG) 88-08 and Eastern Cooperative Oncology Group (ECOG) 4588: Preliminary results of a phase III trial in regionally advanced, unresectable non-small-cell lung cancer. J Natl Cancer Inst 1995; 87: 198-205.

 14. Armstrong JG. Target volume definition for three-dimensional conformal radiation therapy of lung cancer. Br J Radiol 1998; 71: 587-594.

 15. Durrant KR, Berry RJ, Ellis F, et al. Comparison of treatment policies in inoperable bronchial carcinoma. Lancet 1971; 10: 715-719.

 16. Gregor A, Macbeth FR, Paul J, Cram L, Hansen HH. Radical radiotherapy and chemotherapy in localized inoperable non-small-cell lung cancer: A randomized trial. J Natl Cancer Inst 1993; 85: 997-999.

 17. Kaasa S, Thorud E, Host H, Lien HH, Lund E, Sjolie I. A randomized study evaluating radiotherapy versus chemotherapy in patients with inoperable non-small cell lung cancer. Radiother Oncol 1988; 11: 7-13.

 18. Johnson DH, Einhorn LH, Bartolucci A, et al. Thoracic radiotherapy does not prolong survival in patients with locally advanced, unresectable non-small cell lung cancer. Ann Intern Med 1990; 113: 33-38.

 19. Jeremic B, Shibamoto Y, Acimovic L, Milisavljevic S. Hyperfractionated radiation therapy with or without concurrent low-dose daily carboplatin etoposide for stage III non-small-cell lung cancer: A randomized study. J Clin Oncol 1996; 14: 1065-1070.

 20. Trovò MG, Minatel E, Franchin G, et al. Radiotherapy versus radiotherapy enanched by cisplatin in stage III non-small cell lung cancer. Int J Radiat Oncol Biol Phys 1992; 24: 11-15.

 21. Blanke C, Ansari R, Mantravadi R, et al. Phase III trial of thoracic irradiation with or without cisplatin for locally advanced unresectable non-small-cell lung cancer: A Hoosier Oncology Group protocol. J Clin Oncol 1995; 13: 1425-1429.

 22. Anonymous. Postoperative radiotherapy in non-small-cell lung cancer: systematic review and meta-analysis of individual patient data from nine randomised controlled trials. PORT Meta- analysis Trialists Group [see comments]. Lancet 1998; 352: 257-263.

 23. Lederle FA, Niewochner DE. Lung cancer surgery: A critical review of the evidence. Arch Intern Med 1994; 154: 2397-2400.

 24. Morrison R, Deeley TJ, Cleland WP. The treatment of carcinoma of the bronchus: a clinical trial to compare surgery and supervolthage radiotherapy. Lancet 1963; 1: 683-684.

 25. Inculet R, Scott C, Dar AR, et al. Phase III study comparing chemotherapy and radiation therapy with preoperative chemotherapy and surgical resection in patients with non-small cell lung cancer (NSCLC) with spread to mediastinal lymph nodes (N2): A radiation therapy oncology group study (RTOG 89-01). Lung Cancer 1992; 18 (Suppl.1): 65(Abstract)

 26. Canadian Medical Association. The Canadian task force on the periodic health examination. Can Med Assoc J 1979; 121: 1193-1254.

 27. Petrie GJ, Barnwell E, Grimshaw J, on behalf of the Scottish Intercollegiate Guidelines Network. Clinical guidelines: criteria for appraisal for national use. Edinburgh: Royal College of Physicians, 1995.

Figure 4: Ballot 1

LEVEL I: Evidence obtained from meta-analysis of multiple, well-designed, controlled studies. Randomized trials with low false positive and low false negative errors (high power)

LEVEL II: Evidence obtained from at least one well-designed experimental study. Randomized trials with high false positive and/or negative errors (low power)

LEVEL III: Evidence obtained from well-designed, quasi-experimental studies such as non-randomized, controlled single-group, pre-post, cohort, time, or matched case control series

LEVEL IV: Evidence from well-designed, non-experimental studies such as comparative and correlational descriptive and case studies

LEVEL V: Evidence from case reports and clinical examples

Figure 5: Ballot 2

Figure 6: Ballot 3

Legend: CT=chemotherapy, RT=radiotherapy, CT-RT=chemo-radiotherapy, SURG.=surgery +/- (neo-) adjuvant treaments

Figure 7: Ballot 4

Legend: CT=chemotherapy, RT=radiotherapy, CT-RT=chemo-radiotherapy, SURG.=surgery +/- (neo-) adjuvant treaments

Figure 8: Ballot 5

Legend: CT=chemotherapy, RT=radiotherapy, CT-RT=chemo-radiotherapy, SURG.=surgery +/- (neo-) adjuvant treaments

Figure 9: Ballot 6