IMRT evidencias clinicas

Evidencia clínica Evidencia clínica en IMRTen IMRT

Ignacio Sisamón.

Lancet Oncol 2008; 9: 367–375

IMRTIMRTTumores de

Cabeza y Cuello.

Ignacio Sisamón.

Tumores de Cabeza y Cuello.

-Incremento de Toxicidad en regímenes QT-RT-Mucositis – Xerostomia – Disfagia – Fibrosis

IMRT

-Delineación de volúmenes blanco

-Gradiente de dosis entre órgano blanco y OAR.

- Reparar estructuras críticas

Disminuir la toxicidadIncrementar el control local


• Toxicidad y Calidad de Vida.


• Nasofaringe.

• Supervivencia global a 5 años en todos los estadios 50-70%

• Mejor Control local para estadios tempranos (T1-T2) 70-100%

• Mayor toxicidad de RT-QT vs RT sola.– Al Sarrraf. Intergroup 0099. JCO 1998; 16: 1310-17.

• 147 pts, estadios III-IV, RT vs QT-RT. QT-RT mejoró SG a 3 años.



UCSF experience.

2000 — "Three-dimensional intensity-modulated radiotherapy in the treatment of nasopharyngeal carcinoma: the University of California-San Francisco experience." Sultanem K et al. Int J Radiat Oncol Biol Phys. 2000 Oct 1;48(3):711-22.

65-70/2.12-2.25 Gy/day to GTV (including + LN), 60/1.8 Gy per day to CTV, 50-60 Gy to the negative neck.

4-year local PFS was 97%, local-regional PFS 98%, and DM-free rate 66%. 4-year OS 88%

2002 — "Intensity-modulated radiotherapy in the treatment of nasopharyngeal carcinoma: an update of the UCSF experience." Lee N et al. Int J Radiat Oncol Biol Phys. 2002 May 1;53(1):12-22.


2004 - Dose constraints

Prescription dose 70 Gy at 2.12 Gy/fx (33 fx) to GTV, 59.4 Gy at 1.8 to PTV.Int J Radiat Oncol Biol Phys. 2004 Jul 1;59(3):886-96.


68 pts (93.8% WHO tipo 2-3). 70/59.4 Gy (2.12/1.8Gy x fx). If T2b+ or N+ concurrent cisplatin, adjuvant cisplatin/5-FU.

Outcome: Prescribed IMRT given to 84%; prescribed chemo 65%.2-year LC 93%, LRC 89%, DMFR 85%. 2-year PFS 93%, OS 80%.

Acute grade 4 mucositis occurred in 4.4%, worst late grade 3 toxicities: esophagus 4.7%; mucous membranes 3.1%; xerostomia, 3.1%. grade 2 xerostomia at 1 year from start of IMRT was 13.5%.2 patients complained of grade 3 xerostomia, and none had grade 4 xerostomia.

25 pts stage IIB to IVB NPC.

67.5/2.25Gy to post-CT GTV, 54-60 Gy at 1.8-2 Gy/fx to hr-CTV48/1.6Gy to elective neck.

Median follow-up of 29 months

Retrospective. 50 patients, T3-T4 NPC (Stage III 28%, Stage IVA/B 72%). IMRT dose: GTV 76 Gy (whole NP, tumor extending outside NP, skull-base erosions, intracranial disease),

PTV 70 Gy, enlarged LNs 72 Gy, all given in 35 fractions. 34 patients concurrent cisplatin. Median F/U 2.1 years

Outcome: 2-year LRC 96%, DM-free 94%, DFS 93%, OS 92%. 4 recurrences: 2 LR and 2 DM # All patients with recurrence did not have chemo.

Toxicity: 1 treatment-related death from adjuvant chemo; 2 late carotid pseudoaneurysms with torrential epistaxis

Conclusion: Dose-escalation to 76 Gy combined with chemo is feasible in T3-T4 NPC


• Función salival y Xerostomía.


• Función salival y Xerostomia.• Prince of Wales Hospital; 2007 (Hong Kong)(2001-2003) -- "Prospective randomized study of IMRT

on salivary gland function in early-stage nasopharyngeal carcinoma patients." • (Kam MK, J Clin Oncol. 2007 Nov 1;25(31):4873-9.)

– Randomized. 60 patients with T1-2bN0-1 nasopharynx. – Arm 1) IMRT 66 Gy (CTV=GTV + 1cm; at-risk anatomic sites; LN Levels IB-II, LN upper Level V,

LN retropharyngeal; PTV=CTV+3mm), lower neck LN+ 66 Gy anterior field, LN- 54-60 Gy + intracavitary BT boost VS Arm 2) 66 Gy 2D + intracavitary BT boost

– Outcome: observer-related severe xerostomia IMRT 39% vs. 2D-RT 82%, but no difference in patient-reported feeling of xerostomia

– Conclusion: IMRT superior in preserving objective parotid function, but no difference in patient-reported benefit

– Editorial : Observer-rated scoring underestimates patient reports and has low agreement among various observers. Suspect sparing of parotid alone not sufficient. Parotid gland produces saliva without mucins (lubricants, bind water, and provide selective permeability barrier). Mucin-secreting glands (e.g. minor salivary glands, submandibular glands) produce <10% saliva but >50% mucins. May need to spare these glands as well for subjective feeling of benefit

Función salival y Xerostomia.

PARSPORT Trial. First results of a phase III multicenter randomized controlled trial of IMRT vs conventional RT in head and neck cancer.Nutting C, A’Hern R, Rogers MS, et al. Proc Am Soc Clin Oncol 2009; 27 (suppl 18): abstr LBA6006

Role of IMRT in reducing xerostomia in 94 (47 RT; 47 IMRT) pts with H&N cancer. Primary endpoint: incidence of LENTSOMA ≥G2 xerostomia one year after treatment. Secondary endpoints: acute toxicities (CTCAE v3) and other late RTOG and LENT-SOMA radiation toxicities.

12 month LENT-SOMA ≥G2 xerostomia: 74% of RT and 40% of IMRT patients (P=0.005). 12 month ≥G2 xerostomia: 64% RT vs. 41% IMRT patients (P=0.06). 18 months values were 71% and 29% (P=0.004). On the RTOG scale the 18-month incidence was 81% for RT versus 20% for IMRT (P<0.001).

No differences in acute mucositis or pain scores were seen. At 12 months, no statistically significant differences were seen in other late toxicities.

No differences were observed between OS and locoregional control (LRC) rates. IMRT significantly reduces the incidence of xerostomia in pts with pharyngeal tumors


Tumores de Cabeza y Cuello.-

• Función salival y Xerostomia.

Queen Mary Hospital; 2006 (Hong Kong)(2000-2004) -- "Xerostomia and quality of life after IMRT vs. conventional RT for early-stage nasopharyngeal carcinoma: initial report on a randomized controlled clinical trial."

• Pow EH, Int J Radiat Oncol Biol Phys. 2006 Nov 15;66(4):981-91.

– Randomized. 51 patients, Stage II (T2N0-1, AJCC 1997).– Arm 1) conventional RT 68 Gy, neck 66 Gy vs. Arm 2) IMRT, GTV dose 68-72 Gy, PTV 66-68

Gy. Stimulated whole (SWS) and parotid (SPS) saliva flow evaluated, QoL SF-36, EORTC Core, EORTC QLQ-H&N35 questionnaires. Minimum F/U 1 years

– 1-year outcome: 25% whole flow (SWS) IMRT 50% vs. 2D 5% (SS), 25% parotid flow (SPS) 83% vs. 9% (SS).

– At 2 months, both group had xerostomia, but IMRT group improved significantly better over time. Also improvements in QoL

– Conclusion: IMRT significantly better than conventional RT for salivary function and QoL


• Disfagia


• DisfagiaLangendijk, Radiother Oncol. 2009:


• Senos paranasales.

• Supervivencia global (5 años) en todos los estadios 40%

• Control local a 5 años 60%.

• Alta tasa de efectos adversos (35% lesiones visuales y auditivas)



• Cavidad Oral, Orofaringe, Hipofaringe.

QT concurrente, • Escalada dosis, • Fraccionamientos alterados.

• Supervivencia global• Control local

• IMRT tratamiento eficaz con EA leves y mejor calidad de vida.

Aumento en toxicidad aguda y crónica



Retrospective. 20 larynx and 11 hypopharynx patients, treated with IMRT and concurrent platinum-based chemo. Most Stage IV disease. Median F/U 2.2 years

RT dose painting GTV 70/2.12 Gy/fx, high-risk CTV 59.4/1.8 Gy/fx, (typically Levels II-IV; Levels I or V not routinely contoured unless judged high risk), low-risk CTV 54/1.64 Gy/fx (uninvolved contralateral neck and base of skull). Chemo cisplatin 100 mg/m2 Q3W or carbo 60-70 mg/m2 + 5-FU 600 mg/m2.

Outcome: 2-year LC 86%, RC 94%, laryngectomy-free 89%, DM-free 92%, OS 63%.Toxicity: No late G2+ xerostomia. PEG-dependent hypopharynx 31% vs. larynx 15%

Conclusion: IMRT + chemo encouraging LR control in advanced larynx/hypopharynx. However, high rate of PEG dependency

IMRTIMRTTumores

Ginecológicos.

Ignacio Sisamón.

Tumores Ginecológicos.

Irradiación de la pelvis + Braquiterapia

Irradiacion de cadenas para-Aorticas

Combinacion con Quimioterapia

Intestino delgado – Recto – Vejiga Toxicidad hematológica



IMRT disminuye toxicidad gastrointestinal y genitourinaria; aguda y crónica.•Greven KM, Lanciano RM, Herbert SH, et al. Analysis of complications in patients with endometrial carcinoma receiving adjuvant irradiation. Int J Radiat Oncol Biol Phys 1991;21: 919e923.•Yamazaki A, Shirato H, Nishioka T, et al. Reduction of late complications after irregularly shaped four-field whole pelvic radiotherapy using computed tomographic simulation compared with parallel-opposed whole pelvic radiotherapy. Jpn J Clin Oncol 2000;30:180e184.•Mundt AJ, Lujan AE, Rotmensch J, et al. Intensity-modulated whole pelvic radiotherapy in women with gynaecologic malignancies. Int J Radiat Oncol Biol Phys 2002; 52: 1330–37.•Mundt AJ, Roeske JC, Lujan AE, et al. Initial clinical experience with intensity-modulated whole-pelvis radiation therapy in women with gynecologic malignancies. Gynecol Oncol 2001; 82: 456–63.•Mundt AJ, Mell LK, Roeske JC. Preliminary analysis of chronic gastrointestinal toxicity in gynecology patients treated with intensity-modulated whole pelvic radiation therapy. Int J Radiat Oncol Biol Phys 2003; 56: 1354–60.•Chen MF, Tseng CJ, Tseng CC, Kuo YC, Yu CY, Chen WC. Clinical outcome in posthysterectomy cervival cancer patients treated with concurrent cisplatin and intensity- modulated pelvic radiotherapy: comparison with conventional radiotherapy. Int J Radiat Oncol Biol Phys 2007; 67: 1438–44.

Reduce la tasa de toxicidad hematológica.•Lujan AE, Mundt AJ, Yamada SD, et al. Intensity-modulated radiotherapy as a means of reducing dose to bone marrow in gynecologic patients receiving whole pelvic radiotherapy. Int J Radiat Oncol Biol Phys 2003;57:516e521.•Brixey CJ, Roeske JC, Lujan AE, et al. Impact of intensitymodulated radiotherapy on acute hematologic toxicity in women with gynecologic malignancies. Int J Radiat Oncol Biol Phys 2002;54:1388e1396.


IMRT vs no-IMRT mostraron Tasas de Control Local a 1 año comparables.Chen MF, Tseng CJ, Tseng CC, Kuo YC, Yu CY, Chen WC. Clinical outcome in posthysterectomy cervival cancer patients treated with concurrent cisplatin and intensity- modulated pelvic radiotherapy: comparison with conventional radiotherapy. Int J Radiat Oncol Biol Phys 2007; 67: 1438–44.

Campo extendido a para-Aorticos concomitante con QT.•Beriwal S, Gan GN, Heron DE, et al. Early clinical outcome with concurrent chemotherapy and extended-field, intensitymodulated radiotherapy for cervical cancer. Int J Radiat Oncol Biol Phys 2007;68:166e171.•Salama JK, Mundt AJ, Roeske J, et al. Preliminary outcome and toxicity report of extended-field, intensity-modulated radiation therapy for gynecologic malignancies. Int J Radiat Oncol Biol Phys 2006;65:1170e1176.•Esthappan J, Mutic S, Malyapa RS, et al. Treatment planning guidelines regarding the use of CT/PET-guided IMRT for cervical carcinoma with positive paraaortic lymph nodes. Int J Radiat Oncol Biol Phys 2004;58:1289e1297.•Gerszten K, Colonello K, Heron DE, et al. Feasibility of concurrent cisplatin and extended field radiation therapy (EFRT) using intensity-modulated radiotherapy (IMRT) for carcinoma of the cervix. Gynecol Oncol 2006;102:182e188.

El Boost Integrado de forma Simultanea.… para reemplazar la Braquiterapia.… para luego sumar la Braquiterapia.… para pacientes limitados a recibir Braquiterapia.


Mundt AJ, Roeske JC, Lujan AE, et al. Initial clinical experience with intensity-modulated whole-pelvis radiation therapy in women with gynecologic malignancies. Gynecol Oncol 2001; 82: 456–63.

Mundt AJ, Mell LK, Roeske JC. Preliminary analysis of chronic gastrointestinal toxicity in gynecology patients treated with intensity-modulated whole pelvic radiation therapy. Int J Radiat Oncol Biol Phys 2003; 56: 1354–60.

Beriwal S, Jain SK, Heron DE, et al. Clinical outcome with adjuvant treatment of endometrial carcinoma using intensity-modulated radiation therapy. Gynecol Oncol 2006; 102: 195–99.

Bouchard M, Nadeau S, Gingras L, et al. Clinical outcome of adjuvant treatment of endometrial cancer using aperture-based intensity-modulated radiotherapy. Int J Radiat Oncol Biol Phys 2008; 71: 1343–50.

IMRTIMRTTumor de Mama.

Ignacio Sisamón.

Tumores de Mama.

Dificultades de conformación de dosis

Heterogeneidad de dosis en Volumen Irradiado.

Toxicidad cutánea aguda y crónica

Toxicidad pulmonar

Toxicidad cardiovascular

Tumores de Mama.

Tumores de Mama.

The control arm patients were 1.7 times more likely to have a change in breast appearance than the IMRT arm patients after adjustment for year of photographic assessment (95% confidence interval 1.2–2.5, p = 0.008).

Tumores de Mama.

RTC Phase III to compare conventional (tangential field) fractionated whole breast treatment (Arm A) vs accelerated partial breast irradiation plus intensity-modulated radiotherapy (Arm B).

259 pts were randomized and treated. The mean value of the ratio PTV/ipsilateral breast volume was 21%. The rate of G1 and G2 acute skin toxicity: 22% and 19% in Arm A, respectively. Tolerance in Arm B was excellent with only 5% G1 and 0.8% G2 acute skin toxicity.The planning constraints were fully satisfied in most patients.

259 pts were randomized and treated. The mean value of the ratio PTV/ipsilateral breast volume was 21%. The rate of G1 and G2 acute skin toxicity: 22% and 19% in Arm A, respectively. Tolerance in Arm B was excellent with only 5% G1 and 0.8% G2 acute skin toxicity.The planning constraints were fully satisfied in most patients.

Mar del PlataMar del Plata

IMRTIMRTTumores

Cerebrales Primarios.

Ignacio Sisamón.

Tumores de SNC

Iuchi T, Hypofractionated high-dose irradiation for the treatment of malignant astrocytomas using simultaneous integrated boost technique by IMRT. Int J Radiat Oncol Biol Phys 2006; 64: 1317–24.

Fuller CD, Standard fractionation IMRT of primary and recurrent glioblastoma multiforme. Radiat Oncol 2007; 2: 26.

Tasas similares de SG asi como de EA.

Mejoria en SG y SLP a 1 y 2 años.

Tumores de Sistema Nervioso Central.

Patients received conformal radiotherapy after definitive surgery (125 patients had undergone gross total, 17 near total, and 11 subtotal resection). Doses of 59,4 Gy (n=131) or 54,0 Gy (n=22) were prescribed to a 10 mm margin around the target volume. We have used the term conformal radiotherapy to refer to conformal and IMRT.

IMRTIMRTTumores de Tórax.

(pulmón y mesotelioma)

Ignacio Sisamón.

Tumores de Torax.

Semin Thorac Cardiovasc Surg. 2009 Summer;21(2):159-63.

Radiation therapy options for malignant pleural mesotheliomaBaldini, EH

Department of Radiation Oncology, Dana-Farber/Brigham and Women's Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts 02115, USA.

The role of radiation therapy (RT) in the curative treatment of malignant pleural mesothelioma remains undefined.

No data clearly support treatment of unresected mesothelioma with definitive RT.

Early reports showed that RT was associated with unacceptable toxicity, but recent limited data suggest that treatment with intensity-modulated radiation therapy (IMRT) may be tolerable

The Memorial Sloan-Kettering Cancer Center matched photon/electron technique is associated with acceptable efficacy and toxicity, but is limited in that it does not achieve complete coverage of the target volume to the prescription dose.

The best dosimetry is achieved using IMRT, and this approach is the most promising to date. For these reasons, physicians should exercise caution, and IMRT after extrapleural pneumonectomy is probably best offered only by experienced teams or on protocol until further data have been gathered.

New techniques such as helical tomotherapy and/or IMRT with the addition of electrons may also have a role in future treatment.RT can palliate symptoms provided the disease is confined to a tolerable radiation field.

IMRTIMRTTumores

Gastrointestinales.

Ignacio Sisamón.

Tumores Gastrointestinales.

CANAL ANAL.

Multicenter; 2007 (2000-2006) -- "Concurrent chemotherapy and IMRT for anal canal cancer patients: a multicenter experience." (Salama JK, J Clin Oncol. 2007 Oct 10;25(29):4581-6.

Prospective. 53 patients (62% T-2, 67% N0, 15% HIV+) treated with concurrent chemo (5-FU/mitomycin, or FU alone) and RT. Primary sites and involved LN median 51.5 Gy, pelvis and inguinal LN median 45 Gy. Median F/U 14 months

Toxicity: Grade 3 GI 15%, dermatologic 38%; Grade 4 leukopenia 30%, neutropenia 34%. Treatment break in 41%, median 4 days

Conclusion: Effective, and compares favorably with historical standards

U Chicago, 2005 “IMRT in the treatment of anal cancer: toxicity and clinical outcome." Milano MT et al. Int J Radiat Oncol Biol Phys. 2005 Oct 1;63(2):354-61.

IMRT remarkably well tolerated, with minimal toxicity.


Pelvic regions and inguinal nodes receiving 45 Gy.

Primary sites and Involved nodes were boosted to 51.5 Gy.

53 patients were treated with concurrent chemotherapy andIMRT Median follow-up was 14.5 months (range, 5.2 to 102.8 ms)

Tumores Gastrointestinales.CANAL ANAL.

Grade 4 diarrhea occurred in 1 of 8 (13%) patients. The remaining toxicities were grade 1 or 2.


Am J Clin Oncol 2008;31: 264–270

stage II or III rectal adenocarcinoma received capecitabine and SIB-IMRT delivering 55/2.2Gy to GTV simultaneously delivering 45/1.8Gy to regional lymph nodes and areas at risk for harboring microscopic disease. Total mesorectal excision followed 6 weeks later.

8 patients were evaluable. Median follow-up of 26 months (range, 15–40), all patients were alive without evidence of recurrent disease. The crude pCR rate was 38% with 50% achieving down-staging. Of 3 patients who had tumors within 5 cm of the anal verge, 2 underwent sphincter-sparing procedures.

RECTO

Tumores Gastrointestinales.PANCREAS

Wayne State; 2004 — "Intensity-modulated radiotherapy and concurrent capecitabine for pancreatic cancer.“ Ben-Josef E et al. Int J Radiat Oncol Biol Phys. 2004 Jun 1;59(2):454-9.

Retrospective. 15 pts (7 post-surgical, 8 unresectable). IMRT in 25 fx - 45 Gy to lymph nodes, and 45-54 Gy (post-op) or 54 Gy (unresectable) to tumor bed or tumor.Well tolerated.

Tumores Gastrointestinales.PANCREAS

The PARC study is designed as an open, controlled, prospective, randomized phase II trial. Patients in study arm A will be treated with chemoradiation using IMRT combined with gemcitabine and simultaneous cetuximab infusions.

The median total dose for the GTV is to be 54.0/2.16 Gy and for the CTV 45.0/1.8 Gy.

BMC Cancer 2005, 5:131

Health & Medicine

IMRT evidencias clinicas